Workplace conflicts and knowledge hiding: Mediating role of relational psychological contract breach.

This study explains workplace conflicts (interpersonal and task-related) as antecedents of knowledge-hiding behaviors. Moreover, a relational psychological contract breach is a mediator between workplace conflicts and knowledge-hiding behavior. For empirical evidence, data were collected from research and development institutions in Pakistan. The results confirm the significant association between conflicts and knowledge-hiding behaviors and the mediating role of relational psychological contract breach. The objective of this study is to investigate the impact of workplace conflicts (interpersonal conflict and task-related conflict) on knowledge-hiding behaviors (evasive hiding, playing dumb, and rationalized hiding). Besides, a relational psychological contract breach is used as a mediator between workplace conflicts and knowledge-hiding behaviors. By using a simple random sampling technique and time lag strategy, the data were collected from 408 employees working in research and development institutions in Pakistan. For analyses, this study employed partial least squares structural equation modeling statistical technique by using SmartPls-3 software. The results of the study confirm the significant relationship between workplace conflicts and knowledge-hiding behaviors. Relational psychological contract breach also significantly mediates the relationship between conflicts and knowledge-hiding behaviors. However, this study found an insignificant association between interpersonal conflict and evasive knowledge hiding.

Impact of ambient air pollution on outdoor employees' performance: Mediating role of anxiety.

This paper aims to examine the direct and indirect impact of ambient air pollution (AAP) on employees' performance. This study has used cross sectional survey design to collect the data from the outdoor employees of the pharmaceutical industry of Pakistan. The data were collected in time lags from 299. Partial least squares- structural equation modeling (PLS-SEM) approach was applied to analyze the data. The results show that AAP has a significant negative impact on the employees' performance, and anxiety partially mediates the association between AAP and employees' performance. This study reveals that AAP brings anxiety among outdoor employees, which in turn decreases their working performance. The implications, limitations, and future research directions are presented in the last section of this study.

Ethical behaviors by leaders act as a stimulant to the wellbeing of employees by restraining workplace embitterment.

Prior studies have revealed that leaders' ethical behaviors significantly influence employees' wellbeing. However, it's unclear how to increase the positive impact of leaders' ethical behaviors on employees' wellbeing by overseeing the negative workplace emotion. So, this study examines the salient concern of leaders' ethical behaviors that affect employees' negative emotions (workplace embitterment) and, consequently, their wellbeing according to appraisal theories of emotions. The study also investigates the active role of followers' core self-evaluation in moderating the impact of leaders' ethical behaviors on followers' emotions and wellbeing via the mediational chain. Data is collected in two-time intervals with 6 weeks interims through a structured questionnaire from 398 academics of public sector universities in Pakistan. The structured equation modeling and Process Macro 2017 are the tools for data analysis. Findings of this study show that (1) ethical behaviors by leaders have a negative impact on employee workplace embitterment, (2) workplace embitterment completely mediates the association between ethical behaviors of leaders and employee wellbeing, and (3) when leaders do not exhibit ethical behaviors, workplace embitterment is lessened showing high core self-evaluations by employees. In addition, the study findings also reveal that employees' core self-evaluation moderates the effect of leaders' ethical behaviors through workplace embitterment. This study validates the significant role of a leader's ethical behaviors in nourishing employee wellbeing by preventing negative emotions. The study is also significant as it examines how followers' attribute core self-evaluation: (1) can be a substitute for leaders' ethical behaviors and (2) can actively modify the effect of leaders' ethical behaviors on followers' negative emotions and then wellbeing. The study also discussed its contributions in theory and to organizations.

Determinants of Investment Behavior in Mutual Funds: Evidence From Pakistan.

This paper aimed to provide empirical evidence on the behavior of the investor toward mutual funds by considering its relationship with risk perception (RP), return perception (Return P), investment criteria (IC), mutual fund awareness (MFA), and financial literacy (FL). Data were collected using a questionnaire from 500 mutual fund investors, from which 460 questionnaires were used for the analysis. In addition, the snowball sampling technique was used to collect data from different cities in Pakistan. The result showed that RP, Return P, and MFA are insignificant and negatively affect the behavior of mutual fund investors. Investment criteria have a negative and significant effect on the behavior of mutual fund investors. Financial literacy has a positive and insignificant effect on the behavior of mutual fund investors. The results provide better information and guidance to investors and policymakers on the factors that affect the behavior of mutual fund investors.

How Ingratiation Links to Counterproductive Work Behaviors: The Roles of Emotional Exhaustion and Power Distance Orientation.

Ingratiation is regarded as a powerful impression tactic that helps ingratiator achieve their intended goals. Although there is evidence that the consequences of ingratiation are not always positive, little research considers the dark effect of ingratiation on the ingratiator. Based on conservation of resources theory, we develop and test a model that links employees' ingratiation to their counterproductive work behaviors. Data were collected from 216 supervisor-employee dyads. The results of examination with Mplus showed that ingratiation had a positive effect on counterproductive work behaviors, and emotional exhaustion played a mediating role in this relationship. Power distance orientation negatively moderated the relationship between ingratiation and emotional exhaustion and the indirect effect of emotional exhaustion on the relationship between ingratiation and counterproductive work behaviors. Our findings raise attention on the consequences of ingratiation for employees and the dark side of ingratiation for organization.

Workplace Interactional Demands and Work-Family Enrichment: An Investigation From the Service Sector.

Emotional labor has, so far, been found to have negative consequences for service sector employees' personal well-being. This study strives to look at the positive aspect of emotional labor in the interactive jobs. This research focuses on employees' psychological needs fulfillment through workplace interactions. The current research is an effort to highlight the importance of workplace interactions through fulfilling the employees' need for relatedness and personal accomplishment, which triggers positive resources that can be transferred from work domain to home domain and might induce work-family enrichment. Primary data were gathered through self-administered questionnaires. The target population was nurses working in public and private hospitals located in Faisalabad, Lahore, and Multan cities of the province of Punjab, Pakistan. This sector needs the attention of the policymakers if we want to enhance the performance of health sector employees and to improve their work-home enrichment as a healthy worker is a productive worker. Demographic characteristics of respondents have been identified through SPSS while Structural Equation Modeling (SEM) was used as multivariate data analysis tool for statistical analysis. Assessment of measurement and structural model was found satisfactory. The results showed that workplace interactional demands had a significant positive effect on work-family enrichment. Moreover, relatedness and personal accomplishment partially mediated the relationship between workplace interactional demands and work-family enrichment. The findings of the study revealed that workplace interactions are critical in fulfilling the basic psychological needs of individuals and as a result, they find themselves energized and achieve their full potential through the fulfillment of their need for relatedness and accomplishment. This energy is a valuable resource that can enrich their family life.

Job-Related and Nonjob-Related Gossips Among Low-Ranked Employees in Unionized Service Organization.

Workplace incivility is a common phenomenon that is frequently found across all organizations and cultures. This study was planned to investigate the impact of workplace incivility on job and non-job related gossips through the mediating role of cynicism and psychological contract violation. The perspective of low-ranked unionized employees was explored through a survey method by using stratified sampling in eight strata, which were formulated based on geographical distribution. A total of four hundred questionnaires were distributed among the employees of eight circles, 50 from each, while use able responses remained 301. SmartPLS was used to analyze the data through structural equation modeling. From a theoretical perspective, this study has made several contributions by investigating the impact of workplace incivility in the South Asian context and documenting the impact of incivility from the perspective of individuals belonging to minority socio-cultural status. Besides supporting existing literature, this study provided a unique argument that low-ranked employees in South Asian societies do not spread nonjob-related gossips. This finding is contradictory to the existing literature; and, thus, calls for future research to identify this inconsistency. Limitations and future directions are also discussed.

Natural tripeptide capped pH-sensitive gold nanoparticles for efficacious doxorubicin delivery both in vitro and in vivo.

Nanobiotechnology has been gaining ever-increasing interest for the successful implementation of chemotherapy based treatment of cancer. Gold nanoparticles (AuNPs) capped with a natural pH-responsive short tripeptide (Lys-Phe-Gly or KFG) sequence are presented herein for significant intracellular delivery of an anti-cancer drug, doxorubicin (DOX). A particularly increased apoptotic response has been observed for DOX treatments mediated by KFG-AuNPs when compared with drug alone treatments in various cell lines (BT-474, HeLa, HEK 293 T and U251). Furthermore, KFG-AuNP mediated DOX treatment significantly decreases cell proliferation and tumor growth in a BT-474 cell xenograft model in nude mice. In addition, KFG-AuNPs demonstrate efficacious drug delivery in DOX-resistant HeLa cells (HeLa-DOXR).

The Mediating Role of Psychological Need Thwarting in the Relationship Between Compulsory Citizenship Behavior and Psychological Withdrawal.

This study examined a novel process underlying the relationship between compulsory citizenship behavior and psychological withdrawal. Specifically, based on basic psychological needs theory, thwarting of autonomy and relatedness needs were expected to explain the association between compulsory citizenship behavior and psychological withdrawal. The PROCESS macro was used to analyze the data collected from 368 clerical staff working in public universities in Pakistan. The results confirmed that thwarting of autonomy and relatedness need mediated the relationship between compulsory citizenship behavior and psychological withdrawal. This study makes a significant contribution to the unexplored domain of the process employees use to cope with compulsory citizenship behavior. It also highlights the role of an understudied construct, i.e., psychological need thwarting as a crucial motivational mechanism for elucidating the relationship between compulsory citizenship behavior and psychological withdrawal. The findings of this study provide recommendations for future researchers, along with its implications for practitioners.

Organizational Politics And Workplace Deviance In Unionized Settings: Mediating Role Of Job Stress And Moderating Role Of Resilience.

BACKGROUND: Politics and political behaviors are a vicious and bitter reality in an organization's life. Although under investigation for more than three decades, the literature lacks sufficient studies investigating culture-specific potential factors which have the potency to moderate the poisonous consequences of organizational politics. The aim of this study was to investigate the relationship of organizational politics and deviance in unionized settings with the moderating role of resilience in unionized employees in higher power distance culture. METHODS: A cross-sectional design was followed for data collection. The population of this study was low-ranked employees having union identity and working in the largest power distribution company of Pakistan. Stratified sampling was applied, and eight strata's were considered on the basis of geographical distribution, a total of 400 questionnaires were distributed among the employees of eight circles, fifty from each. Smart PLS.3.2.0 was used to analyze data through Structural Equation Modeling (SEM) under measurement and structural models. CONCLUSION: From a theoretical perspective, this study confirmed that employees tend to show interpersonal deviance when they experience organizational politics, but organizational politics does not promote organizational deviance. Under stress, the individual also shows a slightly higher level of interpersonal deviance as compared to organizational deviance. However, the moderating role of resilience has not been proved in this study. Research limitations and future directions have also been discussed.

The paradox role of extraversion in the cross-cultural adjustment process of Asian expatriates.

BACKGROUND: The purpose of this study is to present a broad-brush picture based on empirical evidence on the role of hindrance stressors, motivation, and cultural novelty in expatriate adjustment. Drawing on trait activation theory, this study examines the moderating role of extraversion in enhancing cultural adjustment to achieve positive work engagement and organizational citizenship behavior (OCB) by expatriates. METHODS: We gathered data using a sample of 458 eastern expatriates with current international assignments in different countries around the world. They completed questionnaires sent to them using online platforms for expatriates. RESULTS: The results reveal that hindrance stressors and intrapersonal motivation significantly predict adjustment. Adjustment plays a partially mediating role in achieving OCB and expatriate work engagement. However, this work engagement is stronger when adjustment is used as a mediating factor. Surprisingly, our results provided paradox role of extraversion in predicting adjustment which was somewhat in contradiction to our hypothesized direction of moderating effect. CONCLUSION: Our research puts forward strategies for international business organizations when assigning business expatriates, especially in novel cultures. Our research provides valuable information about expatriates' context for international organizations planning for the accomplishment of their assignments in distant cultures.

Chemopreventive and anti-breast cancer activity of compounds isolated from leaves of Abrus precatorius L.

The present study focuses on isolation and evaluation of the anti-cancer activity of compounds from the leaves of Abrus precatorius. The bioassay-directed strategy was adopted using chromatographic, gas chromatographic-mass spectrum analysis, nuclear magnetic resonance and X-ray crystallography techniques for purification and characterization of active cytotoxic compounds. Further, MDA-MB-231 breast cancer cell lines and 7,12-dimethylbenz (a) anthracene (DMBA) induced virgin female Sprague Dawley (SD) rats were used for in vitro and in vivo cytotoxicity evaluation. Stigmasterol hemihydrate and 9,12-Octadecadienoic acid (Z,Z)-2-hydroxy-1-(hydroxymethyl)ethyl ester or (ß-monolinolein) were the two main cytotoxic constituents of leaf extract of A. precatorius, with an IC50 value of 74.2 and 13.2 µg/ml, respectively, in MDA-MB-231 cells. Additionally, the treatment with the stigmasterol and ß-monolinolein as a combinatorial drug therapy in DMBA-induced female SD rats led to recovery of body weight, decreased tumor weight and volume, without any toxic side effects. Immunohistochemical examination showed extensive cell death and low proliferation in the treated tumor tissues that was confirmed by results from H and E staining, TUNEL assay and Ki-67 index as compared to control animal group. The reversion of glycoprotein, lysosomal and tumor marker enzyme levels back to near-normal levels after treatment with the plant compounds clearly demonstrated the reduction of tumor burden in these animals. This is the first report on isolation and characterization of the two active cytotoxic components from leaves of A. precatorius. Additionally, the profound cytotoxic and tumor-suppressive effect of these two compounds as a combinatorial therapy provide an alternative option for breast cancer treatment.

Transcriptional activator DOT1L putatively regulates human embryonic stem cell differentiation into the cardiac lineage.

BACKGROUND: Commitment of pluripotent stem cells into differentiated cells and associated gene expression necessitate specific epigenetic mechanisms that modify the DNA and corresponding histone proteins to render the chromatin in an open or closed state. This in turn dictates the associated genetic machinery, including transcription factors, acknowledging the cellular signals provided. Activating histone methyltransferases represent crucial enzymes in the epigenetic machinery that cause transcription initiation by delivering the methyl mark on histone proteins. A number of studies have evidenced the vital role of one such histone modifier, DOT1L, in transcriptional regulation. Involvement of DOT1L in differentiating pluripotent human embryonic stem (hES) cells into the cardiac lineage has not yet been investigated. METHODS: The study was conducted on in-house derived (KIND1) and commercially available (HES3) human embryonic stem cell lines. Chromatin immunoprecipitation (ChIP) was performed followed by sequencing to uncover the cardiac genes harboring the DOT1L specific mark H3K79me2. Following this, dual immunofluorescence was employed to show the DOT1L co-occupancy along with the cardiac progenitor specific marker. DOT1L was knocked down by siRNA to further confirm its role during cardiac differentiation. RESULTS: ChIP sequencing revealed a significant number of peaks characterizing H3K79me2 occupancy in the proximity of the transcription start site. This included genes like MYOF, NR2F2, NKX2.5, and HAND1 in cardiac progenitors and cardiomyocytes, and POU5F1 and NANOG in pluripotent hES cells. Consistent with this observation, we also show that DOT1L co-localizes with the master cardiac transcription factor NKX2.5, suggesting its direct involvement during gene activation. Knockdown of DOT1L did not alter the pluripotency of hES cells, but it led to the disruption of cardiac differentiation observed morphologically as well as at transcript and protein levels. CONCLUSIONS: Collectively, our data suggests the crucial role of H3K79me2 methyltransferase DOT1L for activation of NKX2.5 during the cardiac differentiation of hES cells.

Genetic and Epigenetic Profiling Reveals EZH2-mediated Down Regulation of OCT-4 Involves NR2F2 during Cardiac Differentiation of Human Embryonic Stem Cells.

Human embryonic (hES) stem cells are widely used as an in vitro model to understand global genetic and epigenetic changes that occur during early embryonic development. In-house derived hES cells (KIND1) were subjected to directed differentiation into cardiovascular progenitors (D12) and beating cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and differentiated (D12 and 20) cells was undertaken by microarray analysis. ChIP and sequential ChIP were employed to study role of transcription factor NR2F2 during hES cells differentiation. Microarray profiling showed that an alteration of about 1400 and 1900 transcripts occurred on D12 and D20 respectively compared to D0 whereas only 19 genes were altered between D12 and D20. This was found associated with corresponding expression pattern of chromatin remodelers, histone modifiers, miRNAs and lncRNAs marking the formation of progenitors and cardiomyocytes on D12 and D20 respectively. ChIP sequencing and sequential ChIP revealed the binding of NR2F2 with polycomb group member EZH2 and pluripotent factor OCT4 indicating its crucial involvement in cardiac differentiation. The study provides a detailed insight into genetic and epigenetic changes associated with hES cells differentiation into cardiac cells and a role for NR2F2 is deciphered for the first time to down-regulate OCT-4 via EZH2 during cardiac differentiation.

Evaluation of unexplored pomegranate cultivars for physicochemical characteristics and antioxidant activity.

The aim of present study was to evaluate the different pomegranate cultivars for physicochemical properties and to identify the best cultivars suitable for food processing and future breeding. Various attributes of fruit (including length, weight and diameter), rind (thickness and weight), calyx (length), aril (weight, percentage, length and width), seed (length and width) and juice (titratable acidity and soluble solids or TSS) were evaluated. Total and reducing sugar, pH, ascorbic acid, total phenolic contents, antioxidant activity and maturity index were also evaluated. A significant difference in all tested parameters was noted amongst the tested cultivars except calyx length, rind thickness, arils and seed dimensions. The antioxidant activity and total phenolic contents of pomegranate cultivars were ranged from 15.77 to 42% and 1158.9 to 1540.7 mg GAE L-1. The cultivars Tor-390 and Sorkhak-859 were sweet in taste, while the rest of the cultivars have sweet sour taste. The study concluded that the majority of cultivars were rich source of total phenolics, ascorbic acid, total soluble solid and total sugars, which are beneficial to health. Some of the elite cultivars (NKP-561, SRK-296, SZR-385, SRK-878) showed high quality attributes and were suitable for future breeding programs.

EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis.

Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization. Here, we reveal a defective molecular switch in head and neck squamous cell carcinoma (HNSCC). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIAPH1 and FSTL1. DIAPH1, a miR-198 target, enhances directional migration through sequestration of Arpin, a competitive inhibitor of Arp2/3 complex. FSTL1 blocks Wnt7a-mediated repression of extracellular signal-regulated kinase phosphorylation, enabling production of MMP9, which degrades the extracellular matrix and facilitates metastasis. The prognostic significance of the FSTL1-DIAPH1 gene pair makes it an attractive target for therapeutic intervention.

Salicylic acid confers salt tolerance in potato plants by improving water relations, gaseous exchange, antioxidant activities and osmoregulation.

BACKGROUND: Potato is an important vegetable; however, salt stress drastically affects its growth and yield. A pot experiment was therefore conducted to assess salicylic acid efficacy in improving performance of potato cultivars, grown under salt stress (50 mmol L-1 ). Salicylic acid at 0.5 mmol L-1 was sprayed on to potato plants after 1 week of salinity application. RESULTS: Salt stress effects were ameliorated by salicylic acid effectively in both the studied cultivars. N-Y LARA proved more responsive to salicylic acid application than 720-110 NARC, which confirmed genetic variation between cultivars. Salicylic acid scavenged reactive oxygen species by improving antioxidant enzyme activities (superoxide dismutase, catalase, peroxidases) and regulating osmotic adjustment (proline, phenolic contents), which led to enhanced water relation and gaseous exchange attributes, and thereby increased potassium availability and reduced sodium content in potato leaves. Moreover, potato tuber yield showed a positive correlation with potassium content, photosynthesis and antioxidant enzyme activities. CONCLUSION: Salt tolerance efficacy of salicylic acid is authenticated in improving potato crop performance under salt stress. Salicylic acid effect was more pronounced in N-Y LARA, reflecting greater tolerance than 720-110 NARC, which was confirmed as a susceptible cultivar. Hence salicylic acid at 0.5 mmol L-1 and cultivation of N-Y LARA may be recommended in saline soil. © 2016 Society of Chemical Industry.

Insulin-like growth factor binding protein-2 regulates ß-catenin signaling pathway in glioma cells and contributes to poor patient prognosis.

BACKGROUND: Upregulation of insulin-like growth factor binding protein 2 (IGFBP-2) is often associated with aggressiveness of glioblastoma (GBM) and contributes to poor prognosis for GBM patients. In view of the regulation of ß-catenin by IGFBP-2 in breast cancer and the crucial role of ß-catenin pathway in glioma invasion, proliferation and maintenance of glioma stem cells, the mechanism of regulation of ß-catenin by IGFBP-2, and its role in GBM prognosis was studied. METHODS: Regulation of the ß-catenin pathway was studied by immunocytochemistry, Western blot analysis, luciferase assays, and real-time RT-PCR. The role of IGFBP-2 was studied by subcutaneous tumor xenografts in immunocompromised mice using glioma cells engineered to express IGFBP-2 and its domains. GBM patient tumor tissues (n = 112) were analyzed for expression of IGFBP-2 and ß-catenin by immunohistochemistry. Survival analysis was performed employing Cox regression and Kaplan-Meier survival analyses. RESULTS: IGFBP-2 knockdown in U251, T98G, and U373 or overexpression in LN229 and U87 cells revealed a role for IGFBP-2 in stabilization of ß-catenin and regulation of its nuclear functions involving integrin-mediated inactivation of GSK3ß. Similar results were obtained upon overexpression of the C-terminal domain of IGFBP-2 but not the N-terminal domain. Subcutaneous xenograft tumors overexpressing either full-length or the C-terminal domain of IGFBP-2 showed larger volume as compared with controls. Coexpression of high levels of IGFBP-2 and ß-catenin was associated with worse prognosis (P = .001) in GBM patients. CONCLUSION: IGFBP-2 potentiates GBM tumor growth by the activation of the ß-catenin pathway through its C-terminal domain, and their coexpression possibly contributes to worse patient prognosis.

Activin-A signaling promotes epithelial-mesenchymal transition, invasion, and metastatic growth of breast cancer.

BACKGROUND: Activins belong to the transforming growth factor-ß (TGF-ß) superfamily of cytokines. Although the role of TGF-ß in cancer progression has been highly advocated, the role of activin signaling in cancer is not well known. However, overexpression of activin-A has been observed in several cancers. AIMS: The gene expression profile indicated higher expression of Activin-A in breast tumors. Hence the aim of this study was to evaluate the status and role of Activin signaling pathway in these tumors. METHODS: Microarray analysis was performed to reveal gene expression changes in breast tumors. The results were validated by quantitative PCR and immunohistochemical analysis in two independent sets of normal and tumor samples. Further, correlation of activin expression with survival and distant metastasis was performed to evaluate its possible role in tumor progression. We used recombinant activin-A, inhibitors, overexpression, and knockdown strategies both in vitro and in vivo, to understand the mechanism underlying the protumorigenic role of this signaling pathway. RESULTS: We report that activin-A signaling is hyperactivated in breast cancers as indicated by higher activin-A, phosphoSMAD2, and phosphoSMAD3 levels in advanced breast cancers. Bone morphogenetic proteins and molecules involved in this signaling pathway were downregulated, suggesting its suppression in breast cancers. Activin-A expression correlates inversely with survival and metastasis in advanced breast cancers. Further, activin-A promotes anchorage-independent growth, epithelial-mesenchymal transition, invasion, angiogenesis, and stemness of breast cancer cells. We show that activin-A-induced phenotype is mediated by SMAD signaling pathway. In addition, activin-A expression affects the tumor-forming ability and metastatic colonization of cancer cells in nude mice. CONCLUSIONS: These results suggest that activin-A has a critical role in breast cancer progression and, hence, targeting this pathway can be a valuable strategy in treating breast cancer patients.

Protumorigenic actions of S100A2 involve regulation of PI3/Akt signaling and functional interaction with Smad3.

S100 family of calcium-binding proteins is commonly upregulated in a variety of tumor types and is often associated with tumor progression. Among several S100 members, altered expression of S100A2 is a potential diagnostic and prognostic marker in cancer. Several reports suggest a role for S100A2 in metastasis. Earlier, our studies established regulation of S100A2 by transforming growth factor-ß (TGF-ß) and its involvement in TGF-ß-mediated cancer cell invasion and migration. However, the molecular mechanisms of S100A2 protumorigenic actions remain unexplored. In the present study, we demonstrate that overexpression of S100A2 in A549 lung cancer cells induced epithelial-mesenchymal transition (EMT) followed by increased invasion, loose colony morphology in soft agar and enhanced Akt phosphorylation (Ser-473). Furthermore, overexpression of S100A2 led to increased tumor growth in immunocompromised mice. In agreement, immunohistochemical examination of resected xenograft tumors established inverse correlation between S100A2 and E-cadherin expression together with activated Akt signaling. Interestingly, our study demonstrates a strong dependence of S100A2 and Smad3 in TGF-ß-induced Hep3B cell EMT and invasion. Most importantly, we demonstrate that these effects of S100A2 are manifested through functional interaction with Smad3, which is enhanced in the presence of high calcium and TGF-ß. S100A2 stabilizes Smad3 and binds to its C-terminal MH2 domain. Additionally, loss of S100A2 attenuates the transcription of TGF-ß/Smad3 target genes involved in tumor promotion, such as PA1-1 and vimentin. Collectively, our findings present the first mechanistic details of S100A2 protumorigenic actions and its involvement in TGF-ß-mediated cancer cell invasion and EMT.