Integrin α3ß1 in hair bulge stem cells modulates CCN2 expression and promotes skin tumorigenesis.
Life Sci Alliance
; 3(7)2020 07.
Article
en En
| MEDLINE
| ID: mdl-32423907
ABSTRACT
Epidermal-specific deletion of integrin α3ß1 almost completely prevents the formation of papillomas during 7,12-Dimethylbenz[ a ]anthracene/12- O -tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage skin carcinogenesis. This dramatic decrease in tumorigenesis was thought to be due to an egress and premature differentiation of α3ß1-depleted hair bulge (HB) stem cells (SCs), previously considered to be the cancer cells-of-origin in the DMBA/TPA model. Using a reporter mouse line with inducible deletion of α3ß1 in HBs, we show that HB SCs remain confined to their niche regardless of the presence of α3ß1 and are largely absent from skin tumors. However, tumor formation was significantly decreased in mice deficient for α3ß1 in HB SCs. RNA sequencing of HB SCs isolated from short-term DMBA/TPA-treated skin showed α3ß1-dependent expression of the matricellular protein connective tissue growth factor (CCN2), which was confirmed in vitro, where CCN2 promoted colony formation and 3D growth of transformed keratinocytes. Together, these findings show that HBs contribute to skin tumorigenesis in an α3ß1-dependent manner and suggest a role of HB SCs in creating a permissive environment for tumor growth through the modulation of CCN2 secretion.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
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Células Madre
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Regulación de la Expresión Génica
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Folículo Piloso
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Integrina alfa3beta1
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Factor de Crecimiento del Tejido Conjuntivo
Límite:
Animals
Idioma:
En
Revista:
Life Sci Alliance
Año:
2020
Tipo del documento:
Article
País de afiliación:
Países Bajos