Integrins and cancer.
Integrins play an important physiologic role in cell adhesion, and accumulating evidence suggests that they also regulate cell growth, proliferation, migration, and apoptosis. A number of congenital and acquired disease states have been associated with integrins, and small-molecule integrin inhibitors have been approved for treatment of benign hematologic diseases. In cancer, aberrant expression with normal-functioning rather than dominant genetic variations of genes coding for integrins has generally been observed. This aberrant expression is mediated through "bidirectional" receptor signaling and interaction with corresponding signals from growth factor signaling pathways, leading to inhibition of apoptosis, induction of cell proliferation, extracellular matrix remodeling, migration, and angiogenesis. From a clinical perspective, a growing number of molecules targeting integrins have been developed for treatment and imaging purposes; clinical studies in melanoma, prostate cancer, and other malignancies are underway. This review summarizes the biology of integrins, the signal transduction pathways they regulate, and their role in different stages of carcinogenesis. Furthermore, it provides a synopsis on the clinical advancements in integrin targeting for therapeutic and imaging purposes in cancer.
Moschos
Stergios J
SJ
Department of Medicine, Division of Hematology/Oncology, Melanoma and Skin Cancer Program, University of Pittsburgh, Cancer Institute, USA.
Drogowski
Laura M
LM
Reppert
Shelley L
SL
Kirkwood
John M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D019281:Dimerization; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010641:Phenotype; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016023:Integrins