NEDD9 Promotes Migration And Invasion In Breast Cacner By Regulating Epithelial-mesencylmal Transition

Purposes: Epithelial-mesenchymal transition (EMT) plays an important role in many biological processes. The latest studies revealed that the triple-negative breast cancer (TNBC) was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types.Here we wished to discern the role of NEDD9 in TNBC progression and the molecular mechanisms by which NEDD9 regulates EMT and promotes invasion in TNBC.Experimental Design: Paraffin-embedded mammary tissue sections were obtained from 84 breast cancer patients in parallel with the surrounding normal breast epithelia. Samples were analyzed for NEDD9 protein expression as well as immunohistochemical evaluation for ER, PR, Her2 and Viminten. In vitro, by using knockdown and ectopic overexpression strategies, we examined the role of NEDD9 in TNBC progression and the molecular mechanisms by which NEDD9 regulates EMT and promotes invasion in TNBC cells.Results and conclusions: We discovered that the expression of NEDD9 was frequently upregulated in TNBC cell lines as well as in primary TNBC tissues. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to EMT program, activated ERK signaling, upregulated the expression of several EMT-inducing transcription factors and promoted interaction of these factors with the E-cadherin promoter.Data presented in this report contribute to the understanding of the mechanisms how NEDD9 promotes EMT, and provide useful clues to the evaluation of the potentiality of NEDD9 as a responsive molecular target for triple-negative breast cancer chemotherapy.