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SRC activates TAZ for intestinal tumorigenesis and regeneration

Title
SRC activates TAZ for intestinal tumorigenesis and regeneration
Authors
Byun M.R.Hwang J.-H.Kim A.R.Kim K.M.Park J.I.Oh H.T.Hwang E.S.Hong J.-H.
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2017
Journal Title
Cancer Letters
ISSN
0304-3835JCR Link
Citation
vol. 410, pp. 32 - 40
Keywords
APCColorectal cancerRegenerationSRCTAZ
Publisher
Elsevier Ireland Ltd
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Proto-oncogene tyrosine-protein kinase Src (cSRC) is involved in colorectal cancer (CRC) development and damage-induced intestinal regeneration, although the cellular mechanisms involved are poorly understood. Here, we report that transcriptional coactivator with PDZ binding domain (TAZ) is activated by cSRC, regulating CRC cell proliferation and tumor formation, where cSRC overexpression increases TAZ expression in CRC cells. In contrast, knockdown of cSRC decreases TAZ expression. Additionally, direct phosphorylation of TAZ at Tyr316 by cSRC stimulates nuclear localization and facilitates transcriptional enhancer factor TEF-3 (TEAD4)-mediated transcription. However, a TAZ phosphorylation mutant significantly decreased cell proliferation, wound healing, colony forming, and tumor formation. In a CRC mouse model, ApcMin/+, activated SRC expression was associated with increased TAZ expression in polyps and TAZ depletion decreased polyp formation. Moreover, intestinal TAZ knockout mice had intestinal regeneration defects following γ-irradiation. Finally, significant correspondence between SRC activation and TAZ overexpression was observed in CRC patients. These results suggest that TAZ is a critical factor for SRC-mediated intestinal tumor formation and regeneration. © 2017 Elsevier B.V.
DOI
10.1016/j.canlet.2017.09.003
Appears in Collections:
약학대학 > 약학과 > Journal papers
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