Early stage cancer cell invasion: signaling, biomarkers and therapeutic targeting.
The process of primary cancer invasion of distant organs is multifactorial and multistep. Successful therapeutic management of invasive cancers remains hampered by the multitude of overlapping signaling pathways that initiate and drive cancer cell migration. A crucial early event by which cancer cells switch from localized to invasive states is initiated by the acquisition of autonomous motile properties; a process driven by dynamic assemblies and disassemblies of multiple focal adhesion, cytoskeleton and motor proteins. Several of the protein complexes involved are tightly regulated through posttranslational modifications and intermolecular collisions with partners that occur in a time- and space-dependent manner. These concerted mechanisms are essential for the regulation of cell shape, cell polarity, and cell motility and migration in response to chemotactic signals. This review summarizes the current knowledge in the field and potential clinical implications for molecular pathology and cancer therapeutics. It is not meant to be comprehensive; aspects related to basic signaling are not dealt with extensively in this review. However, the reader is referred to excellent reviews that provide coverage of these topics.
Behmoaram
Emy
E
Segal Comprehensive Cancer Center, Lady Davis Institute of the Sir Mortimer B. Davis Jewish General Hospital, Department of Medicine, Faculty of Medicine, McGill University, 3755 Cote Ste-Catherine, Montreal, Canada H3T 1E2.
Bijian
Krikor
K
Bismar
Tarek A
TA
Alaoui-Jamali
Moulay A
MA
D014408:Biomarkers, Tumor / Q000032:analysis; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009367:Neoplasm Staging; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D015398:Signal Transduction
D014408:Biomarkers, Tumor