OncoTargets and Therapy (Mar 2019)
The overexpression of Rab9 promotes tumor progression regulated by XBP1 in breast cancer
Abstract
Yansong Liu,1 Xin Wang,2 Zhonghua Zhang,3 Bin Xiao,4 Baoming An,5 Jun Zhang6 1Breast Department, Shandong Cancer Hospital, Affiliated to Shandong University, Shandong, China; 2Breast Department, Yinan Country People’s Hospital, Shandong, China; 3Breast Department, Dongping Country People’s Hospital, Shandong, China; 4Breast Department, Shanxian Hygeia Hospital, Shandong, China; 5Breast Department, Wulian Country People’s Hospital, Shandong, China; 6Breast Department, Zhangqiu Hospital of Chinese Medicine, Shandong, China Background: Rab9 is a small GTPase that localizes to the trans-Golgi Network (TGN) and late endosomes and is involved in the recycling of mannose-6-phosphate receptors (MPRs). Materials and methods: To determine new treatment strategies for breast cancer and to elucidate the mechanism underlying the phenomenon, we investigated the effects of Rab9 in the human breast cancer cell lines MCF7 and MDA-MB-231.Results: We observed that knockdown of Rab9 inhibited the survival and proliferation of MCF7 and MDA-MB-231 cells, whereas Rab9 overexpression facilitated cell survival and proliferation by inducing or suppressing apoptosis. These results were further confirmed by the Bax/Bcl-2 ratio in affected MCF7 and MDA-MB-231 cells, which demonstrated whether the mitochondrial apoptotic pathway was triggered. Furthermore, the AKT/PI3K pathway is implicated in cell growth and survival and Rab9 changed the expression and phosphorylation of PI3K signaling pathway members. XBP1 is a key regulator of Rab9 and further confirmed that Rab9 play important roles in breast cancer tumorigenesis.Conclusion: These data suggest that Rab9 is a good candidate for a novel therapeutic strategy for the treatment of breast cancer. Keywords: transcription factor, proliferation, MCF7, MDA-MB-231
