Multifaceted collagen-DDR1 signaling in cancer

Hua Su; Michael Karin

doi:10.1016/j.tcb.2023.08.003

Multifaceted collagen-DDR1 signaling in cancer

Trends Cell Biol. 2023 Sep 12:S0962-8924(23)00167-8. doi: 10.1016/j.tcb.2023.08.003. Online ahead of print.

Authors

Hua Su¹, Michael Karin²

Affiliations

¹ Institutes of Biomedical Sciences, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: suhua@fudan.edu.cn.
² Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: karinoffice@health.ucsd.edu.

PMID: 37709651
PMCID: PMC10927612 (available on 2025-03-12)
DOI: 10.1016/j.tcb.2023.08.003

Abstract

In addition to immune cells and fibroblasts, the tumor microenvironment (TME) comprises an extracellular matrix (ECM) which contains collagens (COLs) whose architecture and remodeling dictate cancer development and progression. COL receptors expressed by cancer cells sense signals generated by microenvironmental alterations in COL state to regulate cell behavior and metabolism. Discoidin domain receptor 1 (DDR1) is a key sensor of COL fiber state and composition that controls tumor cell metabolism and growth, response to therapy, and patient survival. This review focuses on DDR1 to NRF2 signaling, its modulation of autophagy and macropinocytosis (MP), and its role in cancer and other diseases. Elucidating the regulation of DDR1 activity and expression under different pathophysiological conditions will facilitate the discovery of new therapeutics.

Keywords: DDR1; autophagy; cancer; collagen; collagen receptors; macropinocytosis.

Publication types

Review

Abstract

Publication types

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