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Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

Title
Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling
Author
이수재
Keywords
colorectal cancer therapy; epithelial-mesenchymal transition; HAS2; malignant tumor; TGF-beta
Issue Date
2019-07
Publisher
WILEY
Citation
CANCER SCIENCE, v. 110, NO 7, Page. 2226-2236
Abstract
Hyaluronic acid synthase 2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines. Depletion of HAS2 in HCT116 and DLD1 cells, which express high levels of HAS2, critically increased sensitivity of radiation/oxaliplatin-mediated apoptotic cell death. Moreover, downregulation of HAS2 suppressed migration, invasion and metastasis in nude mice. Conversely, ectopic overexpression of HAS2 in SW480 cells, which express low levels of HAS2, showed the opposite effect. Notably, HAS2 loss-and gain-of-function experiments revealed that it regulates CRC malignancy through TGF-beta expression and SMAD2/Snail downstream components. Collectively, our findings suggest that HAS2 contributes to malignant phenotypes of CRC, at least partly, through activation of the TGF-beta signaling pathway, and shed light on the novel mechanisms behind the constitutive activation of HAS2 signaling in CRC, thereby highlighting its potential as a therapeutic target.
URI
https://onlinelibrary.wiley.com/doi/full/10.1111/cas.14070https://repository.hanyang.ac.kr/handle/20.500.11754/111344
ISSN
1347-9032; 1349-7006
DOI
10.1111/cas.14070
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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