Centre for Cancer Biomarkers CCBIO

CCBIO Seminar

Nuno M. Coelho

Welcome to CCBIO Seminar with speaker Nuno M. Coelho from the Matrix Dynamics Group, University of Toronto. Title: DDR1 expression, collagen-dependent activation and signalling in cancer and tissue fibrosis.


CCBIO seminars logo, background people in a seminar room and a lecturer in front.
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Apart from the interesting talks, the CCBIO seminars are a good way to meet CCBIO members and associates. Please feel free to inform others about this seminar as all are welcome both to the lecture and the pizza get-together afterwards.

Invited speakerNuno M. Coelho from the Matrix Dynamics Group, University of Toronto.

Time: September 28th 2017 at 14:30, Auditorium 4, BBB
Host: Donald Gullberg

Title: "DDR1 expression, collagen-dependent activation and signalling in cancer and tissue fibrosis."


The discoidin domain receptor 1 (DDR1) is a tyrosine kinase, collagen adhesion mechanoreceptor associated with fibrotic conditions of kidney, liver, lung and perivascular tissues. We reported earlier a role for DDR1 in mechanical realignment of collagen by traction forces, which is consistent with the increased expression of DDR1 in several different types of cancer and fibrotic conditions. Our main findings are that DDR1 clustering, activation, and interaction with myosin IIA filaments enhance the collagen tractional remodeling that is important for collagen alignment in cancer and fibrosis. DDR1 overexpression is associated with b1 integrin activation but little is known about the downstream pathways activated by DDR1 that regulate integrin-dependent signals that contribute to tissue fibrosis. We considered that DDR1 contributes to cancer and tissue fibrosis by regulating b1 integrin-dependent, MAPK signaling. DDR1 over-expression reduced ERK phosphorylation 5-fold in cells expressing b1 integrin when plated on collagen, while plating on fibronectin or inhibition of DDR1 phosphorylation with nilotinib rescued ERK phosphorylation. A phospho-site screen indicated that DDR1 activation inhibit b1 integrin-dependent ERK signalling through regulation of the focal adhesion kinase (FAK) autophosphorylation. In FAK null mouse embryonic fibroblasts, and in cells treated with a FAK inhibitor, collagen-induced ERK activation was reduced, indicating that collagen-induced ERK activation is dependent on FAK.  Our data indicate that DDR1 expression and adhesion to collagen control b1 integrin-dependent MAPK signaling that could contribute to cancer and tissue fibrosis.

Nuno M. Coelho and Christopher A. McCulloch