Knockdown on aPKC-ι inhibits epithelial-mesenchymal transition, migration and invasion of colorectal cancer cells through Rac1-JNK pathway
Knockdown on aPKC-ι inhibits epithelial-mesenchymal transition, migration and invasion of colorectal cancer cells through Rac1-JNK pathway
复制标题
敲低aPKC-iota通过Rac1-JNK通路抑制结直肠癌细胞上皮-间质转化、迁移和侵袭
DOI：
10.1016/j.yexmp.2018.11.007
复制
发表时间：
2019-04-01
影响因子：
3.6
通讯作者：
Yang, Hua
中科院分区：
文献类型：
--
作者：
Du, Guang-Sheng;Qiu, Yuan;Yang, Hua
Background. Atypical protein kinase C-iota (aPKC-iota) is an oncogenic factor, and required for the epithelial-mesenchymal transition (EMT) of different types of cancer. Our study aimed to investigate the role of aPKC-iota in the EMT, migration and invasion of colorectal cancer (CRC) cells.Methods: Expression of aPKC-iota was evaluated in CRC cell lines treated with TGF-beta 1 using qPCR and western blot. After aPKC-iota was knocked down using shRNA, migration and invasion abilities of CRC cell lines were evaluated by wound healing assay and transwell assay, respectively. Activation status of downstream signaling factors of aPKC-iota, including Rac1, JNK, STAT3 and beta-catenin, was measured using western blot. Furthermore, auranofin, an aPKC-iota inhibitor, was used to treat CRC cell lines to investigate its possible inhibition on the EMT of CRC cell lines, as well as on the expression of aPKC-iota and its downstream signaling factors.Results: TGF-beta 1 induced the expression of aPKC-iota in CRC cells, and knockdown on aPKC-iota inhibited the TGF-beta 1-induced EMT, migration and invasion of CRC cells. Interestingly, Rac1 GTPase level was decreased when aPKC-iota was knocked down, and overexpression of Rac1G12V rescued the cell EMT, migration and invasion in CRC cells as inhibited by sh-aPKC-iota. Moreover, knockdown on aPKC-iota suppressed the phosphorylation of JNK and STAT3, and nuclear translocation of beta-catenin. The aPKC-iota inhibitor, Auranofin, showed similar inhibitory effects as aPKC-iota knockdown.Conclusion: Knockdown on aPKC-iota inhibited the EMT, migration and invasion of CRC cells through suppressing of Rac1-JNK pathway. Those findings indicate that aPKC-iota may serve as a novel therapeutic target for CRC.
