一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> MedComm >>article

MedComm

IF: 10.7
Download PDF

Salt‐inducible kinase 2 confers radioresistance in colorectal cancer by facilitating homologous recombination repair

Published:28 January 2025 DOI: 10.1002/mco2.70083 PMID: 39877288
Yuan Meng, Shuo Li, Da-Shan Lu, Xue Chen, Lu Li, You-fa Duan, Gao-yuan Wang, Wenlin Huang, Ran-yi Liu

Abstract

Resistance to radiotherapy remains a critical barrier in treating colorectal cancer (CRC), particularly in cases of locally advanced rectal cancer (LARC). To identify key kinases involved in CRC radioresistance, we employed a kinase-targeted CRISPR-Cas9 library screen. This approach aimed to identify potential kinase inhibitors as radiosensitizers. Our screening identified salt-inducible kinase 2 (SIK2) as a critical factor in CRC radioresistance. Increased SIK2 expression correlated with reduced tumor regression and poorer outcomes in LARC patients undergoing neoadjuvant chemoradiotherapy. The depletion of SIK2 significantly enhanced radiation-induced apoptosis and tumor regression. Mechanistically, SIK2 interacts with valosin-containing protein (VCP), promoting its hyperphosphorylation. This modification improves VCP's capacity to extract K48-linked ubiquitin-conjugated proteins from chromatin, thus aiding the recruitment of RPA and RAD51 to DNA damage sites. This mechanism strengthens homologous recombination–mediated DNA repair, which contributes to radioresistance. Importantly, ARN-3236, a SIK2 inhibitor, markedly sensitized CRC cells to radiation both in vivo and in vitro, providing a potential strategy to overcome radioresistance. In summary, our findings reveal a novel mechanism by which SIK2 contributes to the radioresistance of CRC, proposing SIK2 as a potential therapeutic target with its inhibitor significantly enhancing CRC radiotherapy efficacy.

Similar articles

IF:0

The role of thymidine kinase in cancer diseases.

Expert opinion on medical diagnostics Ondrej Topolcan, Lubos Holubec,etc Published: 1 February 2008
IF:5.4

Sodium butyrate in both prevention and supportive treatment of colorectal cancer.

ACS Applied Energy Materials Karolina Ka?mierczak-Siedlecka, Luigi Marano,etc Published: 26 October 2022
IF:5.4

Adenosine-Metabolizing Enzymes, Adenosine Kinase and Adenosine Deaminase, in Cancer.

ACS Applied Energy Materials Galina Zhulai, Eugenia Oleinik,etc Published: 8 March 2022
玉山县| 娱乐| 寻乌县| 鄂州市| 酒泉市| 齐齐哈尔市| 夏邑县| 涞水县| 历史| 图们市| 太白县| 瑞昌市| 三门峡市| 武强县| 大安市| 池州市| 昌宁县| 南丹县| 自治县| 安乡县| 平泉县| 临沧市| 永新县| 德惠市| 武功县| 石狮市| 将乐县| 岑巩县| 福海县| 宜昌市| 邯郸市| 沾化县| 江门市| 新营市| 通山县| 梅河口市| 丁青县| 赤水市| 兴隆县| 定襄县| 长岛县|