The effects of co-designed physical activity interventions in older adults: A systematic review and meta-analysis.

BACKGROUND: Physical activity (PA) declines with age despite the knowledge that physical inactivity is a leading cause of disease, death, and disability worldwide. To better tailor PA interventions to older adults, researchers are turning to the collaborative principles of co-design. The purpose of this systematic review was to compare the effectiveness of co-designed PA interventions and standard care for increasing PA and other health outcomes (i.e., physical function, quality of life, mental health, functional independence, attendance and attrition rates) in older adults. METHODS: A search was conducted in MEDLINE, AgeLine, CINAHL, Embase, and SPORTDiscus. Records were screened by independent pairs of reviewers. Primary research studies conducted among community-dwelling older adults (age 60+) comparing co-designed PA interventions to standard care were considered for inclusion. Controls included wait-list control, usual care, sham interventions, PA interventions without the use of co-design, and no intervention. A random effects meta-analysis was conducted, and the standardized mean difference (SMD) was used to report effect estimates. Quality of evidence was rated using GRADE. RESULTS: Of 16,191 studies screened, eight (N = 16,733) were included in this review. Most studies reported results favouring the effect of co-design on physical activity; however, only two studies (N = 433) could be pooled for meta-analysis resulting in a SMD of 0.28, (95% CI = -0.13 to 0.69; p = 0.19; I2 = 56%) immediately post-intervention. The GRADE quality of evidence was very low. The quantitative analysis of three studies reported improved physical function. CONCLUSION: This review did not demonstrate that co-designed PA interventions are more effective than standard care for increasing PA in older adults; however, evidence was limited and of very low quality. Further well-designed trials are warranted to better understand the impacts of co-designed PA interventions and how to best implement them into practice. TRIAL REGISTRATION: PROSPERO registration number: CRD42022314217.

Defining the challenges and opportunities for using patient-derived models in prostate cancer research.

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.

Immunogenomic Landscape of Neuroendocrine Prostate Cancer.

PURPOSE: Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small-cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared with other prostate cancer types and SCLC. EXPERIMENTAL DESIGN: In this retrospective study, a cohort of 170 patients with 230 RNA-sequencing and 104 matched whole-exome sequencing data were analyzed. Differences in immune and stromal constituents, frequency of genomic alterations, and associations with outcomes were evaluated. RESULTS: In our cohort, 36% of the prostate tumors were identified as CD8+ T-cell inflamed, whereas the remaining 64% were T-cell depleted. T-cell-inflamed tumors were enriched in anti-inflammatory M2 macrophages and exhausted T cells and associated with shorter overall survival relative to T-cell-depleted tumors (HR, 2.62; P < 0.05). Among all prostate cancer types in the cohort, NEPC was identified to be the most immune depleted, wherein only 9 out of the 36 total NEPC tumors were classified as T-cell inflamed. These inflamed NEPC cases were enriched in IFN gamma signaling and PD-1 signaling compared with other NEPC tumors. Comparison of NEPC with SCLC revealed that NEPC had poor immune content and less mutations compared with SCLC, but expression of checkpoint genes PD-L1 and CTLA-4 was comparable between NEPC and SCLC. CONCLUSIONS: NEPC is characterized by a relatively immune-depleted tumor immune microenvironment compared with other primary and metastatic prostate adenocarcinoma except in a minority of cases. These findings may inform development of immunotherapy strategies for patients with advanced prostate cancer.

Lineage plasticity in prostate cancer: Looking beyond intrinsic alterations.

Emergence of small cell prostate cancer is linked to the plasticity of tumour cells and avoidance of environmental pressures. This process is thought to be reversable, however to-date evidence of this has been demonstrated in small-cell prostate cancer. To study the plasticity of prostate tumours, we look to clinical cohorts of patients covering the spectra of malignancy subtypes and utilise in vitro and in vivo models of disease progression. Current models have assisted in the understanding of the extremities of this plasticity, elucidating internal mechanisms and adaptations to stressors through transition to altered cell states. By interrogating the tumour microenvironment and earlier time points, we are beginning to form a deeper understanding of the full spectra of tumour plasticity. It could be proffered that this deeper understanding will lead to better patient outcome, with earlier interventions more likely to reverse plasticity and prevent trans-differentiation to the aggressive, small cell phenotype.

Alterations in homologous recombination repair genes in prostate cancer brain metastases.

Improved survival rates for prostate cancer through more effective therapies have also led to an increase in the diagnosis of metastases to infrequent locations such as the brain. Here we investigate the repertoire of somatic genetic alterations present in brain metastases from 51 patients with prostate cancer brain metastases (PCBM). We highlight the clonal evolution occurring in PCBM and demonstrate an increased mutational burden, concomitant with an enrichment of the homologous recombination deficiency mutational signature in PCBM compared to non-brain metastases. Focusing on known pathogenic alterations within homologous recombination repair genes, we find 10 patients (19.6%) fulfilling the inclusion criteria used in the PROfound clinical trial, which assessed the efficacy of PARP inhibitors (PARPi) in homologous recombination deficient prostate cancer. Eight (15.7%) patients show biallelic loss of one of the 15 genes included in the trial, while 5 patients (9.8%) harbor pathogenic alterations in BRCA1/2 specifically. Uncovering these molecular features of PCBM may have therapeutic implications, suggesting the need of clinical trial enrollment of PCBM patients when evaluating potential benefit from PARPi.

Struggle and failure on clinical placement: a critical narrative review.

BACKGROUND: Clinical placements are crucial to the development of skills and competencies in speech-language pathology (SLP) education and, more generally, a requirement of all health professional training programmes. Literature from medical education provides a context for understanding how the environment can be vital to all students' learning. Given the increasing costs of education and demands on health services, students who struggle or fail on clinical placement place an additional burden on educators. Therefore, if more is known or understood about these students and their experience in relation to the clinical learning environment, appropriate strategies and support can be provided to reduce the burden. However, this literature does not specifically explore marginal or failing students and their experience. AIMS: To review existing research that has explored failing and struggling health professional students undertaking clinical placements and, in particular, SLP students. METHODS & PROCEDURES: A critical narrative review was undertaken. Three electronic databases, ProQuest, CINAHL and OVID (Medline 1948-), were searched for papers exploring marginal and failing students in clinical placement contexts across all health professions, published between 1988 and 2017. Data were extracted and examined to determine the breadth of the existing research, and publications were critically appraised and major research themes identified. MAIN CONTRIBUTION: Sixty-nine papers were included in the review. The majority came from medicine and nursing in the United States and United Kingdom, with other allied health disciplines less well represented. The review identified key themes with the majority of papers focused on identification of at risk students and support and remediation. The review also highlighted the absence of literature relating to the student voice and in the allied health professions. CONCLUSIONS & IMPLICATIONS: This review highlighted the limited research related to failing/struggling student learning in clinical contexts, and only a handful of papers have specifically addressed marginal or failing students in allied health professions. The complexity of interrelated factors in this field has been highlighted in this review. Further research needs to include the student's voice to develop greater understanding and insights of struggle and failure in clinical contexts.

Language and cognitive communication disorder during post-traumatic amnesia: Profiles of recovery after TBI from three cases.

BACKGROUND: There has been limited empirical speech-language pathology (SLP) study of language and cognitive communication during post-traumatic amnesia (PTA) and the early stages after TBI. The purpose of the current research was to explore the potential means and utility of assessing cognitive communication during PTA and the post-acute recovery period. METHOD: This research used a longitudinal mixed methods design to describe language and cognitive communication assessment and recovery profiles of three patients with TBI. Cognitive communication was assessed with repeated standardised and non-standardised methods during PTA (rated with Westmead PTA Scale) and at follow-up 3 months after PTA emergence. RESULTS: All participants demonstrated a profile of language and cognitive communication strengths and weaknesses during PTA and the post-acute period, also evident at follow-up. Improvement occurred gradually throughout PTA, although with individual fluctuation across test occasions. There was no marked change in communication function immediately before and after PTA emergence, indicating that cognitive communication ability and those functions measured on the Westmead PTA Scale (memory and orientation) did not recover at the same rate. CONCLUSION: It was feasible to assess language and cognitive communication throughout PTA and the post-acute period, and early assessment results were relevant to the patient's ongoing communicative function. It is suggested that early and repeated SLP assessment may contribute to the prediction of persisting cognitive communication issues.

Transcription Factor MYB26 Is Key to Spatial Specificity in Anther Secondary Thickening Formation.

Successful fertilization relies on the production and effective release of viable pollen. Failure of anther opening (dehiscence), results in male sterility, although the pollen may be fully functional. MYB26 regulates the formation of secondary thickening in the anther endothecium, which is critical for anther dehiscence and fertility. Here, we show that although the MYB26 transcript shows expression in multiple floral organs, the MYB26 protein is localized specifically to the anther endothecium nuclei and that it directly regulates two NAC domain genes, NST1 and NST2, which are critical for the induction of secondary thickening biosynthesis genes. However, there is a complex relationship of regulation between these genes and MYB26. Using DEX-inducible MYB26 lines and overexpression in the various mutant backgrounds, we have shown that MYB26 up-regulates both NST1 and NST2 expression. Surprisingly normal thickening and fertility rescue does not occur in the absence of MYB26, even with constitutively induced NST1 and NST2, suggesting an additional essential role for MYB26 in this regulation. Combined overexpression of NST1 and NST2 in myb26 facilitates limited ectopic thickening in the anther epidermis, but not in the endothecium, and thus fails to rescue dehiscence. Therefore, by a series of regulatory controls through MYB26, NST1, NST2, secondary thickening is formed specifically within the endothecium; this specificity is essential for anther opening.

Social communication assessment during post-traumatic amnesia and the post-acute period after traumatic brain injury.

BACKGROUND: Social communication impairment is a persisting and debilitating consequence of traumatic brain injury (TBI). However, there has been little empirical speech-language pathology (SLP) study focusing on the early stage of recovery after TBI, including during post-traumatic amnesia (PTA). This research reports on social communication presentation and recovery during late PTA and the post-acute period, assessed with standardized measures. METHOD: Using mixed-methods case study research, four participants with severe TBI were assessed with social communication assessment measures over the later stages of PTA and/or at PTA emergence, and at follow-up three months later. Assessment tools included the Measure of Cognitive Linguistic Abilities Family Questionnaire, the La Trobe Communication Questionnaire and The Profile of Pragmatic Impairment in Communication and included patient and friend/family perspectives. RESULTS: It was possible to identify a profile of social communication disorder on SLP measures for participants during PTA that persisted at follow-up, but with decreased severity. Self and friend/family member ratings of social communication indicated an increased awareness of social difficulty at three months after PTA emergence. CONCLUSION: Findings provided information about presentation and course of recovery of social communication ability for participants in the early stage of rehabilitation after TBI. These findings have implications for timing and methods of SLP assessment during PTA.

Non-destructive determination of floral staging in cereals using X-ray micro computed tomography (µCT).

BACKGROUND: Accurate floral staging is required to aid research into pollen and flower development, in particular male development. Pollen development is highly sensitive to stress and is critical for crop yields. Research into male development under environmental change is important to help target increased yields. This is hindered in monocots as the flower develops internally in the pseudostem. Floral staging studies therefore typically rely on destructive analysis, such as removal from the plant, fixation, staining and sectioning. This time-consuming analysis therefore prevents follow up studies and analysis past the point of the floral staging. RESULTS: This study focuses on using X-ray µCT scanning to allow quick and detailed non-destructive internal 3D phenotypic information to allow accurate staging of Arabidopsis thaliana L. and Barley (Hordeum vulgare L.) flowers. X-ray µCT has previously relied on fixation methods for above ground tissue, therefore two contrast agents (Lugol's iodine and Bismuth) were observed in Arabidopsis and Barley in planta to circumvent this step. 3D models and 2D slices were generated from the X-ray µCT images providing insightful information normally only available through destructive time-consuming processes such as sectioning and microscopy. Barley growth and development was also monitored over three weeks by X-ray µCT to observe flower development in situ. By measuring spike size in the developing tillers accurate non-destructive staging at the flower and anther stages could be performed; this staging was confirmed using traditional destructive microscopic analysis. CONCLUSION: The use of X-ray micro computed tomography (µCT) scanning of living plant tissue offers immense benefits for plant phenotyping, for successive developmental measurements and for accurate developmental timing for scientific measurements. Nevertheless, X-ray µCT remains underused in plant sciences, especially in above-ground organs, despite its unique potential in delivering detailed non-destructive internal 3D phenotypic information. This work represents a novel application of X-ray µCT that could enhance research undertaken in monocot species to enable effective non-destructive staging and developmental analysis for molecular genetic studies and to determine effects of stresses at particular growth stages.

The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes.

KEY MESSAGE: This study highlights the changes in umami-related nucleotide and glutamate levels when the AMP deaminase gene was elevated in transgenic tomato. Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway.

Biphasic regulation of the transcription factor ABORTED MICROSPORES (AMS) is essential for tapetum and pollen development in Arabidopsis.

Viable pollen is essential for plant reproduction and crop yield. Its production requires coordinated expression at specific stages during anther development, involving early meiosis-associated events and late pollen wall formation. The ABORTED MICROSPORES (AMS) transcription factor is a master regulator of sporopollenin biosynthesis, secretion and pollen wall formation in Arabidopsis. Here we show that it has complex regulation and additional essential roles earlier in pollen formation. An inducible-AMS reporter was created for functional rescue, protein expression pattern analysis, and to distinguish between direct and indirect targets. Mathematical modelling was used to create regulatory networks based on wild-type RNA and protein expression. Dual activity of AMS was defined by biphasic protein expression in anther tapetal cells, with an initial peak around pollen meiosis and then later during pollen wall development. Direct AMS-regulated targets exhibit temporal regulation, indicating that additional factors are associated with their regulation. We demonstrate that AMS biphasic expression is essential for pollen development, and defines distinct functional activities during early and late pollen development. Mathematical modelling suggests that AMS may competitively form a protein complex with other tapetum-expressed transcription factors, and that biphasic regulation is due to repression of upstream regulators and promotion of AMS protein degradation.

Speech-language pathologists' perspectives on cognitive communication assessment during post-traumatic amnesia.

PRIMARY OBJECTIVE: There have been few reports of the approaches taken by speech-language pathologists (SLPs) when assessing cognitive communication (CC) during post-traumatic amnesia (PTA) after TBI. This study sought to understand SLPs' rationales for CC assessment during PTA and to examine their perspectives on assessment methods during the early recovery period. METHODS AND PROCEDURES: In this qualitative study, 10 SLPs participated in semi-structured face-to-face or telephone interviews about their rationales and methods for CC assessment during PTA and early recovery. Content analysis was conducted using NVivo software to identify key categories. MAIN OUTCOME AND RESULTS: SLPs reported their reasons for CC assessment as including: (1) Documenting changes and monitoring progress, (2) Feedback to team, family and patient, (3) Diagnosis of communication disorder, (4) Planning and (5) Prognosis. They described conducting ongoing, informal assessment and monitoring of CC, using a combination of standardized and non-standardized measures during PTA, and commenced formal testing after PTA resolution to formulate a baseline level of communication function. CONCLUSIONS: The current study highlighted the importance that SLPs placed on an individualized approach in CC assessment. Findings provided insight into the process of assessment of CC during PTA and the early stage of recovery after TBI.

Linguistic analysis of discourse in aphasia: A review of the literature.

This review examined previous research applications of linguistic discourse analysis to assess the language of adults with aphasia. A comprehensive literature search of seven databases identified 165 studies that applied linguistic measures to samples of discourse collected from people with aphasia. Analysis of methodological applications revealed an increase in published research using linguistic discourse analysis over the past 40 years, particularly to measure the generalisation of therapy outcomes to language in use. Narrative language samples were most frequently subject to analysis though all language genres were observed across included studies. A total of 536 different linguistic measures were applied to examine language behaviours. Growth in the research use of linguistic discourse analysis and suggestions that this growth may be reflected in clinical practice requires further investigation. Future research directions are discussed to investigate clinical use of discourse analysis and examine the differences that exist between research and clinical practice.

A collaborative approach to supporting communication in the assessment of decision-making capacity.

PURPOSE: This paper explores the clinical implications of acquired communication disorders in decisional capacity. Discipline-specific contributions are discussed in a multidisciplinary context, with a specific focus on the role of speech and language pathologists (SLPs). METHOD: Key rehabilitation issues in determining decisional capacity are identified. The impact of communication impairment on capacity is discussed in light of the research literature relating to supportive communication and collaborative practice that respects human rights. RESULTS: Guidelines are presented for professionals involved in the assessment of the decisional capacity of individuals with communication disorders of neurological origin. They guide an assessor through: assessing cognition, language and speech; determining preferred communication domains; and practical strategies and considerations for maximising communication. CONCLUSION: There is a dearth of guidelines available that deal with augmenting and supporting communication of individuals with acquired communication disorders of neurological origin when it comes to assessing legal decision-making capacity. Capacity assessment is a multidisciplinary realm, and the involvement of SLPs is key to maximising the decision-making capacity of these individuals. IMPLICATIONS FOR REHABILITATION: All clinicians have an obligation to maximise client autonomy and participation in decision-making. Assessments of capacity should involve a general cognitive ability assessment, followed by a decision-specific assessment tool or question set for the decision facing the patient. The involvement of speech and language pathologists (SLPs) is key to assess and facilitate capacity determinations in instances of cognitive-communication disorder. Impairments in different aspects of auditory comprehension require different accommodations.

Language and cognitive communication during post-traumatic amnesia: A critical synthesis.

BACKGROUND: There is minimal speech pathology literature on communication presentation during post-traumatic amnesia (PTA) and the early recovery period after traumatic brain injury. While a body of research reports on other cognitive and behavioural functions during PTA, language and/or cognitive communication are not routinely the primary focus of current research literature. OBJECTIVE: This critical synthesis provides an overview of research to date on communication during PTA to inform speech pathology assessment practice and to assist with information provision to the multidisciplinary team and family members. METHODS: A search was conducted of studies reporting on language, cognition, and cognitive communication during the acute, inpatient and early recovery period after TBI. These were examined for relevance to speech pathology practice during PTA and acute confusional state. RESULTS: Historic and recent literature has described types of language and communication impairment during PTA and early recovery after TBI. Recently, aspects of communication impairment during PTA have been found relevant for outcome prediction. Few studies were found originating from speech pathology on communication during PTA. CONCLUSIONS: Communication disruption forms a key feature of PTA. Existing literature indicates that speech pathology monitoring of communication during PTA may be of benefit as part of multidisciplinary team management during early recovery.

FlowerNet: a gene expression correlation network for anther and pollen development.

Floral formation, in particular anther and pollen development, is a complex biological process with critical importance for seed set and for targeted plant breeding. Many key transcription factors regulating this process have been identified; however, their direct role remains largely unknown. Using publicly available gene expression data from Arabidopsis (Arabidopsis thaliana), focusing on those studies that analyze stamen-, pollen-, or flower-specific expression, we generated a network model of the global transcriptional interactions (FlowerNet). FlowerNet highlights clusters of genes that are transcriptionally coregulated and therefore likely to have interacting roles. Focusing on four clusters, and using a number of data sets not included in the generation of FlowerNet, we show that there is a close correlation in how the genes are expressed across a variety of conditions, including male-sterile mutants. This highlights the important role that FlowerNet can play in identifying new players in anther and pollen development. However, due to the use of general floral expression data in FlowerNet, it also has broad application in the characterization of genes associated with all aspects of floral development and reproduction. To aid the dissection of genes of interest, we have made FlowerNet available as a community resource (http://www.cpib.ac.uk/anther). For this resource, we also have generated plots showing anther/flower expression from a variety of experiments: These are normalized together where possible to allow further dissection of the resource.

Propositional idea density in older men's written language: findings from the HIMS study using computerised analysis.

Decline in linguistic function has been associated with decline in cognitive function in previous research. This research investigated the informativeness of written language samples of Australian men from the Health in Men's Study (HIMS) aged from 76 to 93 years using the Computerised Propositional Idea Density Rater (CPIDR 5.1). In total, 60,255 words in 1147 comments were analysed using a linear-mixed model for statistical analysis. Results indicated no relationship with education level (p = 0.79). Participants for whom English was not their first learnt language showed Propositional Idea Density (PD) scores slightly lower (0.018 per 1 word). Mean PD per 1 word for those for whom English was their first language for comments below 60 words was 0.494 and above 60 words 0.526. Text length was found to have an effect (p = <0.0001). The mean PD was higher than previously reported for men and lower than previously reported for a similar cohort for Australian women.

Assessment practices of speech-language pathologists for cognitive communication disorders following traumatic brain injury in adults: an international survey.

PRIMARY OBJECTIVE: This study's objective was to examine the current assessment practices of SLPs working with adults with acquired cognitive communication impairments following a TBI. METHODS AND PROCEDURES: Two hundred and sixty-five SLPs from the UK, the US, Canada, Australia and New Zealand responded to the online survey stating the areas of communication frequently assessed and the assessment tools they use. MAIN OUTCOMES AND RESULTS: SLPs reported that they routinely assessed functional communication (78.8%), whereas domains such as discourse were routinely assessed by less than half of the group (44.3%). Clinicians used aphasia and cognitive communication/high level language tools and tools assessing functional performance, discourse, pragmatic skills or informal assessments were used by less than 10% of the group. The country and setting of service delivery influenced choice of assessment tools used in clinical practice. CONCLUSIONS: These findings have implications for training of SLPs in a more diverse range of assessment tools for this clinical group. The findings raise questions regarding the statistical validity and reliability of assessments currently used in clinical practice. It highlights the need for further research into how SLPs can be supported in translating current evidence about the use of assessment tools into clinical practice.

Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer.

Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here, we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differentiation in a manner that disrupted alveolar progenitor cell populations. Conversely, exogenous transgenic expression of Runx2 in mammary epithelial cells blocked milk production, suggesting that the decrease in endogenous Runx2 observed late in pregnancy is necessary for full differentiation. In addition, overexpression of Runx2 drove epithelial-to-mesenchymal transition-like changes in normal mammary epithelial cells, whereas Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor latency and enhanced overall survival in a mouse model of breast cancer, with Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our results establish a previously unreported function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions. Cancer Res; 74(18); 5277-86. ©2014 AACR.