Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking
- 주제(키워드) epidermis , integrin , Rab25 , skin , squamous cell carcinoma (SCC)
- 등재 SCIE, SCOPUS
- OA유형 Green Accepted
- 발행기관 John Wiley and Sons Ltd
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161382
- 본문언어 영어
- Published As http://dx.doi.org/10.1002/path.5311
- PubMed https://pubmed.ncbi.nlm.nih.gov/31144312
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two-stage skin carcinogenesis model. Xenografting of a Rab25-deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome–tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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