Non-canonical Activation of Receptor Tyrosine Kinases in Cancer Progression.
Receptor tyrosine kinases (RTKs) are known to be key regulators of cancer cell proliferation, migration, invasion and metastatic spread. Ligand-binding to the extracellular domain triggers canonical activation of the intracellular tyrosine kinase domain. In contrast, it has become evident that RTKs are also regulated by non-canonical tyrosine kinase-independent mechanisms via phosphorylation of their serine/threonine residues. In this review, I mainly introduce our recent findings on the non-canonical regulation of epidermal growth factor receptor (EGFR), ErbB2 and erythropoietin-producing hepatocellular receptor A2 (EphA2), and discuss the roles of non-canonical activation of RTKs in cancer progression and resistance to targeted cancer agents. Further characterization of non-canonical regulation will contribute to the development of new target cancer therapies.
Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
Hiroaki
H
Sakurai
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D036104:Receptor, EphA2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D018719:Erb-b2 Receptor Tyrosine Kinases; D012694:Serine; D013912:Threonine; C508053:ERBB2 protein, human