title: RAD51 regulates CHK1 stability via autophagy to promote cell growth in esophageal squamous carcinoma cells.
abstract: The serine/threonine protein kinase CHK1 has been reported to bind to the recombinase RAD51 and facilitates its assembly in DNA damage sites via phosphorylation. However, the role of RAD51 in regulating the expression of CHK1 has never been explored. Here, we show that RAD51 is highly upregulated in esophageal squamous tumor tissues and its DMC1 domain significantly promotes cell growth of esophageal cancer (EC) cells through CHK1. To gain the mechanistic insights, firstly, in the presence of 3-methyladenine (3MA), an autophagy inhibitor, we found that the reduction of CHK1 and the inhibition of cell growth in RAD51-deficient EC109 cells were strikingly restored. Subsequently, the autophagy-related experiments revealed that RAD51 negatively participated in autophagy. Moreover, results from in vitro clonogenic survival assays showed that RAD51 depletion greatly enabled EC cells to resist the autophagy inhibitors 3MA and hydroxychloroquine (HCQ) treatments. Above all, our studies firstly highlight a direct role of RAD51 in autophagy process and characterize its functional domain in cell growth regulation. Moreover, our data firstly shed insights into the possible application of autophagy inhibitors in treating RAD51 overexpressed EC patients.
authors.affiliation: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Central Laboratory, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, 200071, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zhen
authors.affiliation: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory Medicine, Yangpu Hospital of Tongji University, Shanghai, 200090, China. wangmogan@163.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, 200072, China. shengzhou-2005@163.com.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Yang
keywords: Autophagy; CHK1; Cell growth; ESCC; RAD51