Frameshift mutation of UVRAG: Switching a tumor suppressor to an oncogene in colorectal cancer

Autophagy
Shanshan He, Chengyu Liang

Abstract

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths in the Western world. It has a nearly 50% metastasis rate and only a subset of patients respond to current treatment strategy. UVRAG, a key autophagy effector and a guardian of chromosomal stability, is truncated by a frameshift (FS) mutation in CRC with microsatellite instability (MSI). However, the pathological and clinical significance of this UVRAG truncation remains less understood. Our recent study discovered that this FS mutation yields a much shortened form of the UVRAG protein, which counteracts most of the tumor-suppressor functions of wild-type (WT) UVRAG in autophagy, centrosome stability, and DNA repair in a dominant-negative fashion. Whereas this truncated mutation of UVRAG promotes tumorigenesis, epithelial-to-mesenchymal transition, and metastasis, it appears to sensitize CRC tumors to adjuvant chemotherapy, making it a potential molecular marker to individualize therapeutic approach in CRC.

Citations

Mar 24, 2016·Apoptosis : an International Journal on Programmed Cell Death·Dahong YaoJinhui Wang
Jun 18, 2016·Cancer Biomarkers : Section a of Disease Markers·Huangyan ZhouDian Gao
Jul 24, 2020·World Journal of Gastrointestinal Oncology·Jie SunShi-Wu Zhang
Feb 10, 2021·Molecular Metabolism·Min Jeong KimMinna Woo
May 30, 2021·Experimental Gerontology·Francisco Alejandro Lagunas-Rangel
Jun 26, 2021·Frontiers in Oncology·Huamiao ZhouYong Guo

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BETA
xenograft

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