TY - JOUR
T1 - Extracellular matrix as a contextual determinant of transforming growth factor-b signaling in epithelial-mesenchymal transition and in cancer http://www.tandfonline.com/doi/pdf/10.4161/19336918.2014.972788
AU - Cichon, Magdalena A.
AU - Radisky, Derek C.
N1 - Publisher Copyright:
© Magdalena A Cichon and Derek C Radisky.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Extracellular matrix (ECM) provides both structural support and contextual information to cells within tissues and organs. The combination of biochemical and biomechanical signals from the ECM modulates responses to extracellular signals toward differentiation, proliferation, or apoptosis; alterations in the ECM are necessary for development and remodeling processes, but aberrations in the composition and organization of ECM are associated with disease pathology and can predispose to development of cancer. The primary cell surface sensors of the ECM are the integrins, which provide the physical connection between the ECM and the cytoskeleton and also convey biochemical information about the composition of the ECM. Transforming growth factor-b (TGF-b) is an extracellular signaling molecule that is a powerful controller of a variety of cellular functions, and that has been found to induce very different outcomes according to cell type and cellular context. It is becoming clear that ECM-mediated signaling through integrins is reciprocally influenced by TGF-b: integrin expression, activation, and responses are affected by cellular exposure to TGF-b, and TGF-b activation and cellular responses are in turn controlled by signaling from the ECM through integrins. Epithelialmesenchymal transition (EMT), a physiological process that is activated by TGF-b in normal development and in cancer, is also affected by the composition and structure of the ECM. Here, we will outline how signaling from the ECM controls the contextual response to TGF-b, and how this response is selectively modulated during disease, with an emphasis on recent findings, current challenges, and future opportunities.
AB - Extracellular matrix (ECM) provides both structural support and contextual information to cells within tissues and organs. The combination of biochemical and biomechanical signals from the ECM modulates responses to extracellular signals toward differentiation, proliferation, or apoptosis; alterations in the ECM are necessary for development and remodeling processes, but aberrations in the composition and organization of ECM are associated with disease pathology and can predispose to development of cancer. The primary cell surface sensors of the ECM are the integrins, which provide the physical connection between the ECM and the cytoskeleton and also convey biochemical information about the composition of the ECM. Transforming growth factor-b (TGF-b) is an extracellular signaling molecule that is a powerful controller of a variety of cellular functions, and that has been found to induce very different outcomes according to cell type and cellular context. It is becoming clear that ECM-mediated signaling through integrins is reciprocally influenced by TGF-b: integrin expression, activation, and responses are affected by cellular exposure to TGF-b, and TGF-b activation and cellular responses are in turn controlled by signaling from the ECM through integrins. Epithelialmesenchymal transition (EMT), a physiological process that is activated by TGF-b in normal development and in cancer, is also affected by the composition and structure of the ECM. Here, we will outline how signaling from the ECM controls the contextual response to TGF-b, and how this response is selectively modulated during disease, with an emphasis on recent findings, current challenges, and future opportunities.
KW - Cancer
KW - EMT
KW - Extracellular matrix
KW - Fibrosis
KW - Integrins
KW - TGFb
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U2 - 10.4161/19336918.2014.972788
DO - 10.4161/19336918.2014.972788
M3 - Review article
C2 - 25482625
AN - SCOPUS:84921803186
SN - 1933-6918
VL - 8
SP - 588
EP - 594
JO - Cell Adhesion and Migration
JF - Cell Adhesion and Migration
IS - 6
ER -