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Title: Protein disulfide isomerase a4 as a novel therapeutic target of cancer
Authors: Kuo TF
Chen TY
Jiang ST
Chen KW
Chiang YM
Hsu YJ
Liu YJ
Chen HM
Yokoyama KK
Tsai KC
Yeh HH
Chen YR
Yang MT
Yang CY
Yang WC
Contributors: 國立臺灣海洋大學:水產養殖學系
Date: 2017
Issue Date: 2018-03-19T02:02:28Z
Publisher: Oncogene
Abstract: Abstract
Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity. PDIA4 knockdown resulted in opposite outcomes. Moreover, results obtained in mice with spontaneous hepatoma indicated that PDIA4 deficiency significantly reduced hepatic tumorigenesis and cyst formation and increased mouse survival, tumor death, and caspases 3 and 7 activity. Mechanistic studies illustrated that PDIA4 negatively regulated tumor cell death by inhibiting degradation and activation of procaspases 3 and 7 via their mutual interaction in a CGHC-dependent manner. Finally, we found that 1,2-dihydroxytrideca-5,7,9,11-tetrayne, a PDIA4 inhibitor, reduced tumor development via enhancement of caspase-mediated cell death in TSA tumor-bearing mice.
Relation: 36(39)
Appears in Collections:[Department of Aquaculture] Periodical Articles

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