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MARVELD1 interacting with catalase regulates reactive oxygen species metabolism and mediates the sensitivity to chemotherapeutic drugs in epithelial tumors of the reproductive system
Author(s) -
Zhang Chunbin,
Han Fang,
Shi Ming,
Sun Haoxiu,
Li Yiqun,
Ci Yanpeng,
Yao Yuanfei,
Dou Peng,
Akhtar Muhammad luqman,
Nie Huan,
He Jie,
Li Yu
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23024
Subject(s) - biology , reactive oxygen species , cell growth , catalase , microbiology and biotechnology , oxidative stress , cell culture , cytoplasm , cell , cancer research , apoptosis , biochemistry , genetics
Previous investigations have found that MARVEL domain‐containing 1 (MARVELD1) could inhibit tumor cell proliferation and enhance the sensitivity to chemotherapeutic drugs in hepatocellular carcinoma. Hence, it may be a valuable therapeutic target. In the study, we analyzed the responsive changes of MARVELD1 to 25 stress factors and expression of MARVELD1 in epithelial tumors of the reproductive system. We found that MARVELD1 was transferred to the cytoplasm and mitochondria under cell stress. And under cellular stress, the reactive oxygen species (ROS) levels decreased in MARVELD1 expressed cells while increased in the cells of MARVELD1‐specific siRNA treatment. Meanwhile, MARVELD1 overexpression significantly promoted the inhibition of tumor cell proliferation under cellular stress via affecting ROS metabolism, not cell cycle. In xenograft tumor tissues with MARVELD1 expression, the tumor growth was inhibited and accompanied by the lower ROS levels. Furthermore, we identified that MARVELD1 could interact with catalase (CAT) to enhance latter activity and maintain stability. And the enhanced sensitivity to chemotherapeutic drugs clearly depended on the ability of MARVELD1 scavenge the ROS in carcinoma cells of the reproductive system. Our findings clearly explain that MARVELD1 may regulate tumor cell proliferation and sensitivity to chemotherapeutic drugs via reducing the exorbitant ROS. The mechanism was that MARVELD1 interacted with CAT to maintain latter stability, and then ensure continuous ROS scavenge.