The Collagen Receptor Discoidin Domain Receptor 2 Stabilizes SNAIL1 to Facilitate Breast Cancer Metastasis

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2013 May 7

PMID 23644467

Citations 226

Authors

Kun Zhang

Callie A Corsa

Suzanne M Ponik

Julie L Prior

David Piwnica-Worms

Kevin W Eliceiri

Patricia J Keely

Gregory D Longmore

Affiliations

Soon will be listed here.

Abstract

Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 (discoidin domain receptor 2) regulates SNAIL1 stability by stimulating ERK2 activity, in a Src-dependent manner. Activated ERK2 directly phosphorylates SNAIL1, leading to SNAIL1 nuclear accumulation, reduced ubiquitylation and increased protein half-life. DDR2-mediated stabilization of SNAIL1 promotes breast cancer cell invasion and migration in vitro, and metastasis in vivo. DDR2 expression was observed in most human invasive ductal breast carcinomas studied, and was associated with nuclear SNAIL1 and absence of E-cadherin expression. We propose that DDR2 maintains SNAIL1 level and activity in tumour cells that have undergone epithelial-mesenchymal transition (EMT), thereby facilitating continued tumour cell invasion through collagen-I-rich extracellular matrices by sustaining the EMT phenotype. As such, DDR2 could be an RTK (receptor tyrosine kinase) target for the treatment of breast cancer metastasis.

Citing Articles

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Ma Y, Gong H, Cheng L, Zhang D Int J Gen Med. 2025; 18:907-926.

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Aberrant expression of collagen type X in solid tumor stroma is associated with EMT, immunosuppressive and pro-metastatic pathways, bone marrow stromal cell signatures, and poor survival prognosis.

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Discoidin Domain Receptor 2 Contributes to Breast Cancer Progression and Chemoresistance by Interacting with Collagen Type I.

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Aberrant expression of collagen type X in solid tumor stroma is associated with EMT, immunosuppressive and pro-metastatic pathways, bone marrow stromal cell signatures, and poor survival prognosis.

Famili-Youth E, Famili-Youth A, Yang D, Siddique A, Wu E, Liu W bioRxiv. 2024; .

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Comparative evaluation of collagen modifications in breast cancer in human and canine carcinomas.

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