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PMID: 22366781 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Discoidin domain receptor tyrosine kinases: new players in cancer progression.

Cancer metastasis reviews ·Vol. 31 ·No. 1-2 ·2012-06-00 ·Pages 295-321

Valiathan RR, Marco M, Leitinger B, Kleer CG, Fridman R

Abstract

Almost all human cancers display dysregulated expression and/or function of one or more receptor tyrosine kinases (RTKs). The strong causative association between altered RTK function and cancer progression has been translated into novel therapeutic strategies that target these cell surface receptors in cancer. Yet, the full spectrum of RTKs that may alter the oncogenic process is not completely understood. Accumulating evidence suggests that a unique set of RTKs known as the discoidin domain receptors (DDRs) play a key role in cancer progression by regulating the interactions of tumor cells with their surrounding collagen matrix. The DDRs are the only RTKs that specifically bind to and are activated by collagen. DDRs control cell and tissue homeostasis by acting as collagen sensors, transducing signals that regulate cell polarity, tissue morphogenesis, and cell differentiation. In cancer, DDRs are hijacked by tumor cells to disrupt normal cell-matrix communication and initiate pro-migratory and pro-invasive programs. Importantly, several cancer types exhibit DDR mutations, which are thought to alter receptor function and contribute to cancer progression. Other evidence suggests that the actions of DDRs in cancer are complex, either promoting or suppressing tumor cell behavior in a DDR type/isoform specific- and context-dependent manner. Thus, there is still a considerable gap in our knowledge of DDR actions in cancer tissues. This review summarizes and discusses the current knowledge on DDR expression and function in cancer. It is hoped that this effort will encourage more research into these poorly understood but unique RTKs, which have the potential of becoming novel therapeutic targets in cancer.

MeSH Terms
Animals Collagen/metabolism Discoidin Domain Receptors Disease Progression Enzyme Activation Gene Expression Regulation, Neoplastic Humans Molecular Targeted Therapy Mutation Neoplasms/drug therapy,enzymology,genetics Protein Binding Protein Processing, Post-Translational Protein Structure, Tertiary Receptor Protein-Tyrosine Kinases/antagonists & inhibitors,chemistry,genetics,metabolism Receptors, Mitogen/antagonists & inhibitors,chemistry,genetics,metabolism Signal Transduction
Chemicals
Receptors, Mitogen Collagen Discoidin Domain Receptors Receptor Protein-Tyrosine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Valiathan Rajeshwari R
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Marco Marta
Leitinger Birgit
Kleer Celina G
Fridman Rafael
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Article Info
Journal
Cancer metastasis reviews
Abbr.
Cancer Metastasis Rev
ISSN
1573-7233
DOI
10.1007/s10555-012-9346-z
Published
2012-06-00
Pages
295-321
Language
English
Region
Netherlands
NLM ID
8605731
PMCID
PMC3351584
Subset
IM
Grants
NCI NIH HHS · R01 CA125577 · United States
Medical Research Council · G0701121 · United Kingdom
NCI NIH HHS · CA-107469 · United States
NCI NIH HHS · R01 CA061986 · United States
NCI NIH HHS · R01 CA061986-16 · United States
NCI NIH HHS · R01 CA-125577 · United States
NCI NIH HHS · R01 CA-61986 · United States
NCI NIH HHS · R01 CA107469 · United States
Biotechnology and Biological Sciences Research Council · BB/IO11226/1 · United Kingdom
External Links
PubMed source DOI: 10.1007/s10555-012-9346-z PMC Full Text View journal details
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