Advances in regenerated cellulosic aerogel from waste cotton textile for emerging multidimensional applications.

Rapid development of society and the improvement of people's living standards have stimulated people's keen interest in fashion clothing. This trend has led to the acceleration of new product innovation and the shortening of the lifespan for cotton fabrics, which has resulting in the accumulation of waste cotton textiles. Although cotton fibers can be degraded naturally, direct disposal not only causes a serious resource waste, but also brings serious environmental problems. Hence, it is significant to explore a cleaner and greener waste textile treatment method in the context of green and sustainable development. To realize the high-value utilization of cellulose II aerogel derived from waste cotton products, great efforts have been made and considerable progress has been achieved in the past few decades. However, few reviews systematically summarize the research progress and future challenges of preparing high-value-added regenerated cellulose aerogels via dissolving cotton and other cellulose wastes. Therefore, this article reviews the regenerated cellulose aerogels obtained through solvent methods, summarizes their structure, preparation strategies and application, aimed to promote the development of the waste textile industry and contributed to the realization of carbon neutrality.

Higher affinities of fibers with cell receptors increase the infection capacity and virulence of human adenovirus type 7 and type 55 compared to type 3.

IMPORTANCE: HAdV-3, -7, and -55 are the predominant types causing acute respiratory disease outbreaks and can lead to severe and fatal pneumonia in children and adults. In recent years, emerging or re-emerging strains of HAdV-7 and HAdV-55 have caused multiple outbreaks globally in both civilian and military populations, drawing increased attention. Clinical studies have reported that HAdV-7 and HAdV-55 cause more severe pneumonia than HAdV-3. This study aimed to investigate the mechanisms explaining the higher severity of HAdV-7 and HAdV-55 infection compared to HAdV-3 infection. Our findings provided evidence linking the receptor-binding protein fiber to stronger infectivity of the strains mentioned above by comparing several fiber-chimeric or fiber-replaced adenoviruses. Our study improves our understanding of adenovirus infection and highlights potential implications, including in novel vector and vaccine development.

Pembrolizumab combined with anlotinib improves therapeutic efficacy in pulmonary sarcomatoid carcinoma with TMB-H and PD-L1 expression: a case report and literature review.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a unique subtype of non-small cell lung cancer (NSCLC) with a high degree of malignancy and poor therapeutic effects. With the widespread use of immune checkpoint inhibitors (ICIs) in recent years, few studies have reported that immunotherapy is effective against PSC. As a multi-target anti-vascular targeting agent, anlotinib showed a better anti-tumor effect in various cancer species. The paper reported the therapeutic and side effects of pembrolizumab combined with anlotinib in a patient with advanced PSC. Case presentation: This is a 73 year old female patient who underwent thoracoscopy right upper lobectomy and was diagnosed as locally advanced PSC. However, the patient experienced tumor recurrence and metastasis 7 weeks after surgery and was unable to tolerate chemoradiotherapy. Moreover, she detected TP53 mutation and found that tumor mutation burden (TMB) and PD-L1 were high expression. Therefore, the patient received pembrolizumab combined with anlotinib treatment. After 15 cycles of treatment, the tumor significantly shrank with no tumor activity. The evaluation of tumor efficacy is partial response (PR). During the treatment period, she experienced one-degree thyroid-stimulating hormone elevation and two-degree hand-foot syndrome. Pembrolizumab and anlotinib was continued for two years as a maintenance treatment. The patient had a good quality of life and no disease progression was observed. Currently, the patient is still alive without tumor progression and has overall survival exceeding 45 months and toxic side effects were tolerable. Conclusions: Combining ICIs and anti-angiogenic targeted therapy has brought new hope in treating advanced PSC. Additionally, TMB and PD-L1 expression could be potential predictive biomarkers of the efficacy in advanced PSC with immunotherapy.

SARS-CoV-2 mRNA vaccine requires signal peptide to induce antibody responses.

New SARS-CoV-2 variants continue to prevail worldwide, and effective vaccines are needed to prevent an epidemic. mRNA vaccines are gradually being applied to the prevention and control of infectious diseases with significant safety and effectiveness. The spike (S) protein of SARS-CoV-2 is the main target of mRNA vaccine design, but the impact of the signal peptide (SP), transmembrane region (TM), and cytoplasmic tail (CT) on mRNA vaccine remains unclear. In this study, we constructed three forms of mRNA vaccines related to the S protein: full-length, deletion of the TM and CT, and simultaneous deletion of the SP, TM and CT, and compared their immunogenicity. Our experimental data show that full-length S protein and deletion of the TM and CT could effectively induce neutralizing antibody production in mice, while S protein without the SP and TM could not. This indicates that the S protein SP is necessary for the design of mRNA vaccine.

High expression of MORC2 predicts worse neoadjuvant chemotherapy efficacy in triple negative breast cancer.

Tumor infiltrating lymphocytes (TILs) are closely related to the patients' prognosis. Recently, Microrchidia 2 (MORC2) has been documented as a prognostic and predictive biomarker in triple negative breast cancer (TNBC). To compare whether MORC2 is a better predictor than TILs, as well as clinicopathological parameters, in predicting the efficacy of neoadjuvant chemotherapy (NAC) in TNBC, we detected the expression of MORC2 on neoplastic cells through immunohistochemistry and quantified the stromal TILs through Hematoxylin-eosin staining on core biopsies from 50 locally advanced TNBC patients who underwent standard NAC. Among all the 50 patients, 28 (56%) cases had residual tumors, while the other 22 (44%) achieved pathologic complete response (pCR). In these studied patients, age and T-stage showed no correlation with pCR rate, while percentage of TILs, nodal involvement and expression of MORC2 on tumor cells showed significant association with pCR rate. Positive nodal involvement was correlation with worse pathologic response at multivariate analysis (P = .0036), and high TILs levels (≥50%) was positively associated with better NAC efficacy at univariate analysis (P = .002). Whereas high expression of MORC2 was statistically associated with worse pCR rate both at univariate (P < .001) and multivariate (P = .036) analysis. Our results indicate that MORC2 expression has a better predictive role in predicting the efficacy of NAC than TILs in TNBC patients.

Immune checkpoint inhibitor sintilimab-induced lethal myocarditis overlapping with myasthenia gravis in thymoma patient: A case report.

RATIONALE: Immune checkpoint inhibitors have been extensively used and significantly improved the clinical outcomes in multiple types of cancer. But the immune-related adverse events occur frequently, particularly in thymoma. The cardiac immune-related adverse, which is relatively rare but fatal, have been increasing reported. PATIENT CONCERNS: A 45-year-old thymoma patient was admitted to our hospital after receiving anti-programmed cell death-1 treatment with sintilimab 14 days later, accompanied by abdominal pain, intermittent chest tightness and dizziness. DIAGNOSES: The laboratory tests revealed elevated serum troponin I. Electrocardiogram reported the prolongation of QTc interval. Echocardiography showed small amount of pericardial effusion, a left ventricular ejection fraction of 71%. Coronary artery computed tomography angiography revealed localized noncalcified plaque in the middle of the left anterior descending artery and mild stenosis of the lumen. Enhanced computed tomography scanning of the whole abdomen showed no abnormal signs in the parenchyma organs. Combining the results of the examinations, the Immune checkpoint inhibitor induced myocarditis was diagnosed. INTERVENTIONS: The patient was treated with glucocorticoids (120 mg/day, IV, methylprednisolone) within 24 hours of admission. Seven days later, the patient experienced tachy ventricular arrhythmia and cardiogenic shock and was transferred to intensive care unit after electrical cardioversion, tracheal intubation and cardiopulmonary resuscitation. Intravenous immunoglobulin therapy at 25 g/day was given and methylprednisolone was reduced to 40 mg/day for the next 3 days. Intravenous esmolol and lidocaine were used for correcting arrhythmias. Ventilator positive pressure ventilation was used for respiratory support. She was administrated with plasmapheresis when the electrocardiogram monitoring showed ventricular arrhythmia storms. OUTCOME: The patient progressed to ventricular arrhythmia storms and cardiac failure, which eventually resulted in death. LESSONS: The case aims to raise awareness of immune-mediated cardiotoxicity and bring thoughts to the prospects of immunotherapy in thymoma.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Association of hormone receptor status with cardiovascular disease mortality in 399,209 patients with stage I to III breast cancer: A population-based study.

Adjuvant endocrine therapy (AET) is known to reduce the risk of hormone receptor-positive (HR+) breast cancer (BC) recurrence and mortality rates, but its impact on cardiovascular disease (CVD) events is unclear. The primary objective of this study was to analyze the association of HR status with CVD mortality in patients with stage I to III BC. A retrospective study of patients with stage I to III BC was conducted using the 2004 to 2016 Surveillance, Epidemiology, and End Results (SEER) database, and patients were grouped according to their HR status. Propensity score matching (PSM) was used to adjust for heterogeneity between the groups. The cumulative incidence rate of CVD mortality was evaluated via a cumulative incidence curve. Univariate and multivariate Fine and Gray's competing risk regression models were used to identify risk factors associated with CVD mortality. In total, 399,209 patients with BC were included in this study, and 329,958 patients (82.65%) were HR-positive. The cumulative incidence of CVD death was 8.28% in stage I to III BC patients. In the constituent ratio analysis, primary BC was the leading cause of death (45.29%, N = 31,465), followed by heart disease (16.07%, N = 11,166). Compared to the second year following BC diagnosis, the risk of CVD-specific death gradually increased. After PSM, 65,952 pairs of patients were matched, which led to the equilibrium of all variables between the HR-negative cohort and HR+ cohort. Multivariate analysis indicated that HR status was not significantly associated with the risk of CVD mortality, with a hazard ratio of 1.01 (P = .895). This study highlights the importance of understanding the associations between risk factors and CVD for BC patients. HR status was not associated with the risk of CVD mortality in this study.

Deubiquitylase OTUD1 confers Erlotinib sensitivity in non-small cell lung cancer through inhibition of nuclear translocation of YAP1.

Evidence exists suggesting tumor-inhibiting properties of deubiquitylase OTUD1 in various malignancies. We herein investigated the anti-tumor effect and clarified the downstream mechanisms of OTUD1 in the chemoresistance of non-small cell lung cancer (NSCLC) cells. Expression of OTUD1 was examined in NSCLC (PC-9 cells) and erlotinib-resistant NSCLC (PC-9/ER) cell lines. OTUD1 was bioinformatically predicted to be weakly expressed in NSCLC tissue samples and verified in PC-9/ER cells. PC-9/ER cells were subsequently subjected to ectopic expression of OTUD1 alone or combined with SOX9 to dissect out the effect of OTUD1 on the proliferation, chemoresistance and apoptosis in vitro and in vivo. OTUD1 upregulation sensitized NSCLC cells to erlotinib both in vitro and in vivo. In the presence of OTUD1 overexpression, nuclear translocation of YAP1 was inhibited and its expression was inactivated. This effect of OTUD1 was associated with the decreased ubiquitination level of YAP1. SOX9/SPP1 inactivation was the consequence of inhibited nuclear translocation of YAP1. Overexpression of SOX9 reversed the inhibitory effect of OTUD1 on the resistance of NSCLC cells to erlotinib. In conclusion, our study reveals that OTUD1 potentially acts as a tumor suppressor and suppresses erlotinib resistance of NSCLC through the YAP1/SOX9/SPP1 axis, suggesting that OTUD1 may serve as a target for reducing chemoresistance for NSCLC.

Analysis of Hazard Factors Affecting the Quality of Life for Lung Cancer Patients after Chemotherapy.

Objective: To explore the hazard factors affecting the quality of life for patients with lung cancer after chemotherapy, so as to provide evidence-based clinical proof to improve their quality of life. Methods: The clinic data of lung cancer patients treated with chemotherapy from November 2020 to November 2021 in our hospital were selected for retrospective analysis. A questionnaire survey was administered to 74 patients who met the inclusion criteria. The general condition questionnaire made by the department was used to analyzed the patients' demographic characteristics and disease status. The quality of life questionnaire for Chinese cancer patients receiving chemobiotherapy (QLQ-CCC) was used to evaluate the patients' quality of life. Results: The research objects selected for this study scored an average of (94.53 ± 22.65) points in the quality of life. It was found by logistic regression analysis that age, education level, marital status, pathological types, monthly family income, and metastasis were the independent influencing factors that lowered the quality of life of lung cancer patients after chemotherapy (P < 0.001). Conclusion: Chemotherapy can lead to a decline in the quality of life of lung cancer patients, and there are many factors at play. Therefore, medical and nursing staff should focus on the overall condition of patients when carrying out clinical treatment.

Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma.

PURPOSE: Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. MATERIALS AND METHODS: Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. RESULTS: A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. CONCLUSION: Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Inter-annual and intra-annual variations in water quality and its response to water-level fluctuations in a river-connected lake, Dongting Lake, China.

The hydrological conditions of river-connected lakes are complex primarily owing to their considerable water-level fluctuations (WLFs). Water quality in such lakes varies with hydrodynamic variations; however, their relationship is not clear. To identify the unique relationship between water level and water quality in river-connected lakes, we used the comprehensive pollution index (CPI) and regression analysis to analyze the spatiotemporal variation in water quality in Dongting Lake from 2015 to 2018 and the effects of water level on water quality. Four water quality parameters were selected: total nitrogen (TN), total phosphorus (TP), permanganate index (CODMn), and chlorophyll a (Chl-a). The results showed significant spatial variation in the lake water quality, with relatively high concentrations of TN, TP, CODMn, and Chl-a in East Dongting Lake. TN and TP decreased by 12.15% and 37.61%, respectively, from 2015 to 2018, whereas CODMn increased from 1.781 to 2.009 mg/L. Seasonally, TN and TP concentrations were low in the summer and autumn, with high concentrations in the winter and spring. In contrast, CODMn and Chl-a concentrations exhibited opposite trends. The pollution level in Dongting Lake ranged between slightly and moderately polluted, with a CPI ranging from 0.76 to 1.32 across all sampling sites during 2015-2018. The water level in Dongting Lake initially increased and, then, decreased in a year, with marked WLFs owing to seasonal shifts in precipitation and human activities. The water level had significant negative relationships with TN and TP concentrations and a significant positive relationship with CODMn concentration (p < 0.05). Based on the results, strict control of excessive external nutrient loading should be actively implemented in Dongting Lake, in addition to hydrological regulation for effective lake water quality management.

HMGB1-activated fibroblasts promote breast cancer cells metastasis via RAGE/aerobic glycolysis.

Highly expressed high mobility group box-1 protein (HMGB1) promotes tumor metastasis. Whether HMGB1 participates in breast cancer cell activation of fibroblasts is unknown. The culture medium of 6 breast cancer cell lines with different migration potential, and with HMGB1 overexpression or knockdown was used to induce fibroblast activation, and collagen and α-SMA expression were measured. We evaluated the migration potential of MDA-MB-231 cells with fibroblasts treated with 3-PO (3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one) inhibitor, anti-HMGB1 treatment, or RAGE (receptor for advanced glycation end products) knockdown. A lung metastasis murine model was used to evaluate whether the RAGE-knockdown fibroblasts mitigates MDA-MB-231 metastasis. Breast cancer cells that are highly migratory and have a high invasive potential, had higher HMGB1 expression and induced greater fibroblast activation strongly than cells with poorer motility. hrHMGB1 and the supernatants of HMGB1-overexpressed MCF-7 cells promoted fibroblast activation, but loss-HMGB1 of MDA-MB-231 abolished potential. Moreover, a novel mechanism was identified by which HMGB1 facilitated fibroblast activation by RAGE/aerobic glycolysis. Consistently, fibroblasts enhanced MDA-MB-231 metastasis, but the enhancement was reversed by 3-PO inhibition, anti-HMGB1 treatment, or RAGE knockdown in vitro and in vivo. We identified that HMGB1 secreted by breast cancer cells promotes fibroblast activation via RAGE/aerobic glycolysis, and activated fibroblasts enhance breast cancer cell metastasis through increased lactate.

LncRNA GAS5/miR­4465 axis regulates the malignant potential of nasopharyngeal carcinoma by targeting COX2.

Nasopharyngeal carcinoma is a malignant tumor that not only negatively affects the physical and mental health but also the quality of life of the patients. Growth arrest-specific transcript 5 (GAS5) is a common long-chain non-coding RNA (lncRNA) that has been reported to participate in the development of various cancers. However, the biological functions of lncRNA GAS5 in the occurrence and development of nasopharyngeal carcinoma are elusive. The expression of lncRNA GAS5 in nasopharyngeal carcinoma and normal samples were analyzed. Bioinformatic tool was utilized to predict the potential function of lncRNA in nasopharyngeal carcinoma. Transplanted mice were used for in vivo experiments. We observed that the expression of lncRNA GAS5 was upregulated in nasopharyngeal carcinoma tissues and cells. Down-regulation of lncRNA GAS5 inhibited the proliferation and promoted apoptosis of nasopharyngeal carcinoma cells. The expression of miR-4465 was down regulated in nasopharyngeal carcinoma tissues and cells. LncRNA GAS5 could directly bind to miR-4465 and regulated the expression of miR-4465. It was further confirmed that miR-4465 could directly bind with COX2 and inhibit the expression of COX2. Down-regulation of lncRNA GAS5 suppressed tumor growth, promoted the expression levels of miR-18a-5p and suppressed the expression of COX2 in vivo. LncRNA GAS5 regulated nasopharyngeal carcinoma malignancy through targeting miR-4465 and modulating COX2. The GAS5/miR-4465/COX2 axis in nasopharyngeal carcinoma pathogenesis was confirmed, which would provide a new therapeutic target for nasopharyngeal carcinoma.

RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2.

Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was  downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo. In contrast, knockdown of RNF144A promoted malignant phenotypes of breast cancer cells. Quantitative proteomics and biochemical analysis revealed that RNF144A interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. Notably, the ligase activity-defective mutants of RNF144A impaired its ability to induce ubiquitination and degradation of HSPA2, and to suppress breast cancer cell proliferation, migration, and invasion as compared with its wild-type counterpart. Moreover, RNF144A-mediated suppression of breast cancer cell proliferation, migration, and invasion was rescued by ectopic HSPA2 expression. Clinically, low RNF144A and high HSPA2 expression in breast cancer patients was correlated with aggressive clinicopathological characteristics and decreased overall and disease-free survival. Collectively, these findings reveal a previously unappreciated role for RNF144A in suppression of breast cancer growth and metastasis, and identify RNF144A as the first, to our knowledge, E3 ubiquitin ligase for HSPA2 in human cancer.

Ecto-5'-nucleotidase (CD73) is a potential target of hepatocellular carcinoma.

High expression of ecto-5'-nucleotidase (CD73) has been reported in a number of epithelium origin malignancies. Here, we hypothesize that CD73 promotes hepatocellular carcinoma (HCC) growth and metastasis and that the effect is mediated by epithelial growth factor receptor (EGFR). HCC cells with different malignancies and Tissue microarrays of the tumor and peritumoral liver tissues from 30 independent patients were used to examine CD73 and EGFR expression. Then, MTT and Ki67 detection, together with cell adhesion, invasion, and migration assays were used to evaluate the effects of CD73 on cell growth and metastasis. The expression of EGFR in HCC cells was also tested after suppressing or overexpressing CD73. Lastly, tumor tissues from nude mice, which had been injected subcutaneously with HCC cells, were transplanted subcutaneously into CD73-/- and wild-type (WT) C57 mice. CD73 expression was higher in HCC cells with greater metastatic potentials and tumor tissues compared with low metastatic cells and peritumor tissues. CD73 and EGFR were coexpressed and positively correlated in tumor and peritumor liver tissues in HCC tissue microarrays. Up-regulationof CD73 by plasmid transfection or by pharmacological agents promoted EGFR expression in HCC cells, whereas suppression of CD73 inhibited these effects. The growth of transplanted tumor tissues was dramatically slower in CD73-/- mice than in WT type mice in the in vivo experiments. CD73 promotes HCC growth and metastasis and upregulated the expression of EGFR in HCC. Thus, CD73 and EGFR are potential targets in the treatment of HCC.

Epigenetic silencing of RNF144A expression in breast cancer cells through promoter hypermethylation and MBD4.

Emerging evidence shows that ring finger protein 144A (RNF144A), a poorly characterized member of the Ring-between-Ring (RBR) family of E3 ubiquitin ligases, is a potential tumor suppressor gene. However, its regulatory mechanism in breast cancer remains undefined. Here, we report that RNF144A promoter contains a putative CpG island and the methylation levels of RNF144A promoter are higher in primary breast tumors than those in normal breast tissues. Consistently, RNF144A promoter methylation levels are associated with its transcriptional silencing in breast cancer cells, and treatment with DNA methylation inhibitor 5-Aza-2-deoxycytidine (AZA) reactivates RNF144A expression in cells with RNF144A promoter hypermethylation. Furthermore, genetic knockdown or pharmacological inhibition of endogenous methyl-CpG-binding domain 4 (MBD4) results in increased RNF144A expression. These findings suggest that RNF144A is epigenetically silenced in breast cancer cells by promoter hypermethylation and MBD4.

Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target.

CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the ratelimiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation. Its expression is related to many diseases, such as autoimmune diseases, ischemia-reperfusion injuries, arterial calcifications, and atherosclerosis. CD73 is overexpressed in many cancers. Its expression is positively associated with tumor growth, metastasis, angiogenesis, poor prognosis and resistance to chemotherapy. Thus, CD73 may be used for prognostic indicator and therapeutic target in diseases such as cancers.

Extracellular 5'-nucleotidase (CD73) promotes human breast cancer cells growth through AKT/GSK-3ß/ß-catenin/cyclinD1 signaling pathway.

To identify the role and to explore the mechanism of extracellular 5'-nucleotidase (CD73) in human breast cancer growth, CD73 expression was measured firstly in breast cancer tissues and cell lines, and then interfered with or over-expressed by recombinant lentivirus in cell lines. Impacts of CD73 on breast cancer cell proliferation and cell cycle were investigated with colony formation assay, CCK-8 and flow cytometry. The relationship between CD73 and AKT/GSK-3ß/ß-catenin pathway was assessed with adenosine, adenosine 2A receptor antagonist (SCH-58261), adenosine 2A receptor agonist (NECA), CD73 enzyme inhibitor (APCP) and Akt inhibitor (MK-2206). Moreover, the effect of CD73 on breast cancer growth in vivo was examined with human breast cancer transplanting model of nude mice. The results showed that the expression of CD73 was high in breast cancer tissues and increased with advanced tumor grades and lympho-node status. CD73 expression was higher in more malignant cells, and CD73 overexpression promoted breast cancer cell proliferation in both in vivo and in vitro. It activated AKT/GSK-3ß/ß-catenin/cyclinD1 signaling pathway through CD73 enzyme activity and other mechanism.

Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein with emerging roles in the regulation of DNA damage response and gene transcription, but its mechanistic role in breast cancer development and progression remains unexplored. Here, we show that MORC2 promoted breast cancer invasion and metastasis and these effects depended on a proline-rich domain (PRD) within its carboxy-terminal region spanning residues 601-734. Induced expression of wild-type MORC2 did not significantly affect cell proliferation and cell-cycle progression, but promoted breast cancer cell migration and invasion in vitro and metastatic lung colonization in vivo. The PRD domain was dispensable for the protein stability and subcellular localization of MORC2, but depletion of the PRD domain substantially suppressed MORC2-mediated migration, invasion, and metastasis. Proteomic and biochemical analyses further demonstrated that wild-type MORC2, but not PRD deletion mutant, interacted with catenin delta 1 (CTNND1), a cadherin-associated protein that participates in tumor invasion and metastasis. Moreover, knockdown of endogenous CTNND1 by short hairpin RNAs suppressed the migratory and invasive potential of MORC2-expressing cells. Taken together, these results suggest that MORC2 promotes breast cancer invasion and metastasis through its PRD domain-mediated interaction with CTNND1.