|
|||||
|
|
Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals |
|
| Authors: | Xiujuan Qu Ye Zhang Yingchun Li Yingying Xu Kezou Hou Yunpeng Liu |
| Affiliation: | a Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China b Department of Respiratory Medicine, the First Hospital of China Medical University, Shenyang 110001, China c Division of Microbiology, Department of Pathological Sciences, School of Medicine, University of Fukui, Fukui 9101193, Japan |
| Abstract: | The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further investigation revealed that mitochondrial depolarization was enhanced by Cbl-b and decreased by Cbl-b (DN) in RBL-2H3 cells. Moreover, overexpression of Cbl-b significantly suppressed ERK activation, and Cbl-b (DN) strongly enhanced both ERK and Akt activation. Altogether, these results indicate that Cbl-b sensitized both leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial apoptotic pathway and modulating the ERK and Akt survival pathways. |
| Keywords: | Cbl-b Anthracycline PI3K/Akt ERK Leukemia Gastric cancer |
| 本文献已被 ScienceDirect 等数据库收录！ | |