Zhang Jie, Li Xiaorui, Yang Weilong, Jiang Xiaokui, Li Na
Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China.
Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University Xinxiang, Henan 453100, P.R. China.
Oncol Rep. 2014 Sep;32(3):1312-8. doi: 10.3892/or.2014.3304. Epub 2014 Jul 3.
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.
越来越多的证据表明，肿瘤坏死因子受体相关因子4（TRAF4）是一种癌基因，在许多人类癌症中经常过度表达。尽管TRAF4最初是在乳腺癌中被鉴定出来的，但TRAF4在肿瘤发生中的潜在机制在很大程度上仍然未知。在本研究中，我们发现TRAF4在癌细胞中过度表达，并且RNA干扰（RNAi）介导的TRAF4基因敲低降低了细胞生长、细胞迁移和侵袭。接下来，我们发现TRAF4促进细胞存活激酶Akt的膜募集，这对Akt激活至关重要。此外，我们证明了Akt与TRAF4之间存在直接相互作用。另外，组成型激活的Akt的过表达逆转了TRAF4基因沉默细胞中的细胞生长停滞。综上所述，我们的数据表明TRAF4通过与Akt的直接相互作用和激活在乳腺癌的肿瘤发生中起重要作用，这意味着TRAF4可能是乳腺癌预防和治疗的潜在分子靶点。
