Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 227-240 |
| Number of pages | 14 |
| Journal | Journal of Pathology |
| Volume | 249 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2019 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
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Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking. / Jeong, Haengdueng; Lim, Kyung Min; Kim, Kwang H.; Cho, Yejin; Lee, Buhyun; Knowles, Byron C.; Roland, Joseph T.; Zwerner, Jeffrey P.; Goldenring, James R.; Nam, Ki Taek.
In: Journal of Pathology, Vol. 249, No. 2, 01.10.2019, p. 227-240.Research output: Contribution to journal › Article
TY - JOUR
T1 - Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking
AU - Jeong, Haengdueng
AU - Lim, Kyung Min
AU - Kim, Kwang H.
AU - Cho, Yejin
AU - Lee, Buhyun
AU - Knowles, Byron C.
AU - Roland, Joseph T.
AU - Zwerner, Jeffrey P.
AU - Goldenring, James R.
AU - Nam, Ki Taek
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069893073&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069893073&partnerID=8YFLogxK
U2 - 10.1002/path.5311
DO - 10.1002/path.5311
M3 - Article
C2 - 31144312
AN - SCOPUS:85069893073
VL - 249
SP - 227
EP - 240
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 2
ER -