Akt‑mediated phosphorylation of Oct4 is associated with the proliferation of stem‑like cancer cells.
Akt‑mediated phosphorylation of Oct4 is associated with the proliferation of stem‑like cancer cells.
复制标题
DOI：
10.3892/or.2015.3752
复制
发表时间：
2015-04
期刊：
影响因子：
4.2
通讯作者：
Wang YJ
中科院分区：
文献类型：
--
作者：
Zhao QW;Zhou YW;Li WX;Kang B;Zhang XQ;Yang Y;Cheng J;Yin SY;Tong Y;He JQ;Yao HP;Zheng M;Wang YJ
POU 5 F1编码的Oct 4蛋白在维持多能干细胞的自我更新中起着关键作用;然而，它在癌细胞中的存在仍然存在争议。在本研究中，我们提供的证据表明，真正的OCT 4基因（OCT 4A）和它的多个假基因的转录本中检测到的各种癌细胞系。还使用抗Oct 4A单克隆抗体通过蛋白质印迹法检测到一些主要条带。此外，使用抗Oct 4-pT 235抗体来鉴定大多数测试的癌细胞系中与抗Oct 4A条带之一一致的条带，所述条带可被特异性shRNA减少。通过免疫荧光显微镜和免疫组织化学，在人胶质母细胞瘤和肝癌标本中也检测到Oct 4-pT 235信号。在神经干细胞培养基中培养U87胶质母细胞瘤细胞以诱导富含干细胞样癌细胞的神经球的形成。与单层亲本细胞相比，球体细胞中Oct 4-pT 235的水平显著增加，这一结果伴随着PI 3 K-Akt通路的上调。Akt的特异性抑制剂Akti-1/2能有效降低Oct 4-pT 235的表达，抑制U87细胞的增殖。ITE是一种芳香烃受体激动剂，也显著减弱了胶质母细胞瘤和肝癌细胞中Akt介导的Oct 4磷酸化，并降低了异种移植肿瘤模型中的致瘤潜力。综上所述，我们得出结论，Akt介导的Oct 4A或其同源蛋白的磷酸化与干细胞样癌细胞的增殖有关，这可能是某些类型癌症的新生物标志物和药物靶点。
Oct4 protein encoded by POU5F1 plays a pivotal role in maintaining the self-renewal of pluripotent stem cells; however, its presence in cancer cells remains controversial. In the present study, we provided evidence that the transcripts of authentic OCT4 gene (OCT4A) and its multiple pseudogenes were detected in a variety of cancer cell lines. A few major bands were also detected by western blotting using an anti-Oct4A monoclonal antibody. Moreover, an anti-Oct4-pT235 antibody was used to identify a band in the majority of the tested cancer cell lines that coincided with one of the anti-Oct4A bands which was decreasable by a specific shRNA. The Oct4-pT235 signals were also detected in human glioblastoma and liver cancer specimens by immunofluorescence microscopy and immunohistochemistry. U87 glioblastoma cells were cultured in a neural stem cell medium to induce the formation of neurospheres rich in stem-like cancer cells. The levels of Oct4-pT235 in the sphere cells were markedly increased compared to their monolayer parental cells, a result that was accompanied by upregulation of the PI3K-Akt pathway. Akti-1/2, a specific inhibitor of Akt, effectively reduced the level of Oct4-pT235 and attenuated the proliferation of U87 sphere cells. ITE, an agonist of the aryl hydrocarbon receptor, also significantly attenuated the Akt-mediated phosphorylation of Oct4 in glioblastoma and liver cancer cells, and reduced their tumorigenic potential in a xenograft tumor model. Taken together, we concluded that the Akt-mediated phosphorylation of Oct4A or its homolog protein was associated with the proliferation of stem-like cancer cells that may serve as a novel biomarker and drug target for certain types of cancer.
登录
查看更多内容
影响因子：
5.2
作者：
Liu J;Ma L;Xu J;Liu C;Zhang J;Liu J;Chen R;Zhou Y
通讯作者：
Zhou Y
影响因子：
3.8
作者：
Li J;Zhou BP
通讯作者：
Zhou BP
影响因子：
16
作者：
Lin, Yuanji;Yang, Ying;Li, Weihua;Chen, Qi;Li, Jie;Pan, Xiao;Zhou, Lina;Liu, Changwei;Chen, Chunsong;He, Jianqin;Cao, Hongcui;Yao, Hangping;Zheng, Li;Xu, Xiaowei;Xia, Zongping;Ren, Jiangtao;Xiao, Lei;Li, Lanjuan;Shen, Binghui;Zhou, Honglin;Wang, Ying-Jie
通讯作者：
Wang, Ying-Jie
影响因子：
3.7
作者：
Saxe JP;Tomilin A;Schöler HR;Plath K;Huang J
通讯作者：
Huang J
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.