POTEE promotes colorectal carcinoma progression via activating the Rac1/Cdc42 pathway
POTEE promotes colorectal carcinoma progression via activating the Rac1/Cdc42 pathway
复制标题
POTEE 通过激活 Rac1/Cdc42 通路促进结直肠癌进展
DOI：
10.1016/j.yexcr.2020.111933
复制
发表时间：
2020
影响因子：
3.7
通讯作者：
Zhou Jun
中科院分区：
文献类型：
--
作者：
Xu Qiong;Chen Jianxiong;Peng Man;Duan Shiyu;Hu Yukun;Guo Dan;Geng Jian;Zhou Jun
目前的研究表明，POTE锚蛋白结构域家族成员作为肿瘤抗原在恶性肿瘤中有高表达，如前列腺癌、卵巢癌、乳腺癌等。POTEE是POTE锚蛋白家族E.然而，其在结直肠癌（CRC）中的作用尚未研究。本研究首次探讨POTEE在结直肠癌中的作用，并分析其与结直肠癌细胞生物学行为的相关性。定量逆转录-聚合酶链反应（qRT-PCR）、蛋白质印迹和免疫组化显示POTEE在CRC中显著过表达，并与侵袭性表型相关。我们还发现POTEE定位于细胞质中。此外，POTEE表达下调在体外可显著抑制结直肠癌细胞的增殖、迁移和侵袭，在体内可抑制肿瘤的生长和转移。相反，POTEE的过表达可促进CRC细胞的侵袭行为。POTEE通过增加Rac 1和Cdc 42的活化促进CRC迁移、侵袭和上皮-间质转化（EMT）。综上所述，POTEE可能作为大肠癌发生发展的一个癌基因，并可能成为临床诊断和治疗的一个新的分子标志物。
Current studies have shown that POTE ankyrin domain family members have high expressions as tumor antigens in malignant tumors, such as prostate cancer, ovarian cancer, breast cancer and the like. POTEE is a member of the POTE anchor protein family E. However, its role in colorectal carcinoma (CRC) has not been studied. In this study, the function of POTEE in CRC was examined for the first time and its correlation with CRC cell biological behaviors was analyzed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry revealed that POTEE was remarkably overexpressed in CRC and associated with an aggressive phenotype. We also found that POTEE was localized in the cytoplasm. In addition, downregulation of POTEE expression can notably inhibit the proliferation, migration, and invasion of CRC cell in vitro, and repressed tumor growth and metastasis in vivo. In contrast, overexpression of POTEE could promote the aggressive behaviors of CRC cells. Mechanistically, POTEE promoted CRC migration, invasion and epithelial-mesenchymal transition (EMT) by increasing the activation of Rac1 and Cdc42. To summarize, these results suggested that POTEE might serve as an oncogene for CRC tumorigenesis and progression, and may become a novel molecular marker for clinical diagnosis and treatment.