INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling.

Abstract

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.

• Authors: Xufen Ding, Tianwei Chen, Qian Shi, Peng Nan, Xiang Wang, Dong Xie, Jingjing Li
• Journal: Experimental cell research (Exp Cell Res) Vol. 407 Issue 2 Pg. 112826 (Oct 15 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 34508742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• INTS6 protein, human
• RNA-Binding Proteins
• Tumor Suppressor Proteins
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• G1 Phase Cell Cycle Checkpoints
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Mice, Nude
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Prognosis
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Survival Rate
• Tumor Cells, Cultured
• Tumor Suppressor Proteins (genetics, metabolism)
• Xenograft Model Antitumor Assays