TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cellsReportar como inadecuado




TGFβ-mediated suppression of CD248 in non-cancer cells via canonical Smad-dependent signaling pathways is uncoupled in cancer cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 14:113

Cell and molecular biology

Abstract

BackgroundCD248 is a cell surface glycoprotein, highly expressed by stromal cells and fibroblasts of tumors and inflammatory lesions, but virtually undetectable in healthy adult tissues. CD248 promotes tumorigenesis, while lack of CD248 in mice confers resistance to tumor growth. Mechanisms by which CD248 is downregulated are poorly understood, hindering the development of anti-cancer therapies.

MethodsWe sought to characterize the molecular mechanisms by which CD248 is downregulated by surveying its expression in different cells in response to cytokines and growth factors.

ResultsOnly transforming growth factor TGFβ suppressed CD248 protein and mRNA levels in cultured fibroblasts and vascular smooth muscle cells in a concentration- and time-dependent manner. TGFβ transcriptionally downregulated CD248 by signaling through canonical Smad2-3-dependent pathways, but not via mitogen activated protein kinases p38 or ERK1-2. Notably, cancer associated fibroblasts CAF and cancer cells were resistant to TGFβ mediated suppression of CD248.

ConclusionsThe findings indicate that decoupling of CD248 regulation by TGFβ may contribute to its tumor-promoting properties, and underline the importance of exploring the TGFβ-CD248 signaling pathway as a potential therapeutic target for early prevention of cancer and proliferative disorders.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-113 contains supplementary material, which is available to authorized users.

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Autor: Sahana Suresh Babu - Yanet Valdez - Andrea Xu - Alice M O’Byrne - Fernando Calvo - Victor Lei - Edward M Conway

Fuente: https://link.springer.com/







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