INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling.
INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling.
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DOI：
10.1016/j.yexcr.2021.112826
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发表时间：
2021-09
影响因子：
3.7
通讯作者：
Xufen Ding;Tianwei Chen;Q. Shi;P. Nan;Xiang Wang;D. Xie;Jingjing Li
中科院分区：
文献类型：
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作者：
Xufen Ding;Tianwei Chen;Q. Shi;P. Nan;Xiang Wang;D. Xie;Jingjing Li
INTS6（整合子复合体亚基6）已被报道为许多癌症的肿瘤抑制因子。然而，目前尚未研究INTS6在结直肠癌（CRC）中的表达及其生物学功能。本研究中我们发现，与正常组织相比，结直肠癌组织中INTS6的表达明显升高，且与预后不良相关。下调INTS6诱导G1/ s期细胞周期阻滞，显著抑制CRC细胞及其衍生肿瘤的生长，而过表达INTS6则相反。机制研究发现，INTS6增加磷酸化AKT （p-AKT）和ERK （p-ERK）的水平，而AKT和ERK抑制剂抑制了INTS6的促生长作用。此外，INTS6还影响PI3K/AKT和MAPK信号传导的两个靶点c-Myc和CDK2的表达，从而导致细胞周期改变。总之，本研究揭示了INTS6在结直肠癌中的致癌作用，为这种恶性肿瘤的治疗提供了新的靶点。
INTS6 (integrator complex subunit 6) has been reported as a tumor suppressor in many cancers. However, the expression and biological function of INTS6 in colorectal cancer (CRC) has not been investigated yet. In this study, we found that INTS6 expression was significantly increased in CRC tissues when compared with normal tissues and was associated with poor prognosis. Downregulation of INTS6 induced G1/S-phase cell cycle arrest, and markedly suppressed the growth of CRC cells and the derived tumors, while overexpression of INTS6 showed opposite effect. Mechanism study revealed that INTS6 increased the levels of phosphorylated AKT (p-AKT) and ERK (p-ERK), and the growth-promoting effect of INTS6 was inhibited by AKT and ERK inhibitors. Besides, INTS6 also affected the expression of two targets of PI3K/AKT and MAPK signaling, c-Myc and CDK2, which contributed to cell cycle alteration. Altogether, the present study has revealed the oncogenic role of INTS6 in CRC, providing a novel therapeutic target for this malignant cancer.