Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking
| Autor: | Buhyun Lee, Ki Taek Nam, Joseph T. Roland, Byron C. Knowles, Haengdueng Jeong, Kwang H. Kim, Kyung Min Lim, Yejin Cho, Jeffrey P. Zwerner, James R. Goldenring |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Keratinocytes Integrins Mice 129 Strain Skin Neoplasms Integrin Down-Regulation medicine.disease_cause Article Pathology and Forensic Medicine Malignant transformation 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Skin Squamous Cell Carcinoma medicine Animals Humans Neoplastic transformation Cell Proliferation Mice Knockout biology Cell growth Tumor Suppressor Proteins Proteins Tumor Burden Gene Expression Regulation Neoplastic HaCaT Protein Transport 030104 developmental biology Cell culture rab GTP-Binding Proteins 030220 oncology & carcinogenesis biology.protein Cancer research Carcinoma Squamous Cell Carcinogenesis Signal Transduction |
| Zdroj: | J Pathol |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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