ARL2 对于同源重组修复和结肠癌细胞干细胞存活是必需的。

ARL2 is required for homologous recombination repair and colon cancer stem cell survival.

机构信息

College of Pharmacy, Sookmyung Women's University, Seoul, Korea.

Department of Biological Sciences, Sookmyung Women's University, Seoul, Korea.

出版信息

FEBS Open Bio. 2022 Aug;12(8):1523-1533. doi: 10.1002/2211-5463.13438. Epub 2022 May 24.

DOI:10.1002/2211-5463.13438

PMID:35567502

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9340879/

Abstract

ARL2 regulates the dynamics of cytological components and is highly expressed in colon cancer tissues. Here, we report novel roles of ARL2 in the cell nucleus and colon cancer stem cells (CSCs). ARL2 is expressed at relatively low levels in K-RAS active colon cancer cells, but its expression is induced in CSCs. Depletion of ARL2 results in M phase arrest exclusively in non-CSC cultured cells; in addition, DNA break stress accumulates in CSCs leading to apoptosis. ARL2 expression is positively associated with the expression of all six RAD51 family genes, which are essential for homologous recombination repair (HRR). Furthermore, ARL2 is required for HRR and detected within chromatin compartments. These results demonstrate the requirement of ARL2 in colon CSC maintenance, which possibly occurs through mediating double-strand break DNA repair in the nucleus.

摘要

ARL2 调节细胞成分的动态变化，在结肠癌组织中高度表达。在这里，我们报告了 ARL2 在细胞核和结肠癌干细胞（CSC）中的新作用。ARL2 在 K-RAS 活性结肠癌细胞中的表达水平相对较低，但在 CSC 中其表达被诱导。ARL2 的耗竭导致非 CSC 培养细胞中仅出现 M 期停滞；此外，CSC 中 DNA 断裂应激积累导致细胞凋亡。ARL2 的表达与 RAD51 家族的所有六个基因的表达呈正相关，这些基因对于同源重组修复（HRR）至关重要。此外，ARL2 对于 HRR 是必需的，并在染色质区室中被检测到。这些结果表明 ARL2 在结肠 CSC 维持中的必要性，这可能是通过在核内介导双链断裂 DNA 修复来实现的。