title: TRAF4 promotes tumorigenesis of breast cancer through activation of Akt.
abstract: Increasing evidence suggests that tumor necrosis factor receptor-associated factor 4 (TRAF4) is an oncogene which is frequently overexpressed in many human carcinomas. Although TRAF4 was originally identified in breast cancer, the underlying mechanism of TRAF4 in tumorigenesis remains largely unknown. In the present study, we found that TRAF4 was overexpressed in cancer cells, and RNA interference (RNAi)-mediated gene knockdown of TRAF4 decreased cell growth, cell migration and invasion. Next, we found that TRAF4 promoted cell survival kinase Akt membrane recruitment, which is essential for Akt activation. Furthermore, we demonstrated a direct interaction between Akt and TRAF4. Additionally, overexpression of constitutively activated Akt reversed cell growth arrest in TRAF4 gene-silenced cells. Taken together, our data indicate that TRAF4 plays an important role in tumorigenesis of breast cancer through direct interaction and activation of Akt, implying that TRAF4 may be a potential molecular target for breast cancer prevention and therapy.
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University Xinxiang, Henan 453100, P.R. China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053449:TNF Receptor-Associated Factor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D051057:Proto-Oncogene Proteins c-akt