Cell surface adhesion molecules and adhesion-initiated signaling: understanding of anoikis resistance mechanisms and therapeutic opportunities.
Cells express various cell surface adhesion molecules (receptors) that not only mechanically serve as contacting sites between the cell and extracellular matrix (ECM) or adjacent cells, but also initiate intracellular signaling pathways modulating important cellular events including survival and proliferation. Normal cells undergo apoptosis when lacking ECM attachment. This type of cell death has been termed anoikis. Anoikis can be viewed as a normal process which ensures tissue homeostasis and failure to execute the anoikis program or resistance to anoikis could result in adherent cells surviving under suspension condition and proliferating at ectopic sites where the matrix proteins are different from those the cells originally contact. Resistance to anoikis is emerging as a hallmark of metastatic cancers which enables cancer cells to disseminate to distant organs through systemic circulation. In this review, we will discuss the molecular basis of adhesion-initiated signaling, the impact of loss of cell-ECM adhesion on normal cell survival, the role of cancer cell aggregate formation via intercellular adhesion under non-adherent condition, and mechanisms of anoikis resistance developed in metastatic cancer cells. Understanding of these aspects will provide opportunities to find new potential molecular targets, and therapeutic strategies based on these findings will likely prove to be more specific and effective.
Department of Surgery, Section of Pediatric Surgery, and the Riley Children's Hospital, Indiana University School of Medicine, Indianapolis, 46202, IN, USA. Electronic address: xzhong@iupui.edu.
Xiaoling
X
Zhong
Department of Surgery, Section of Pediatric Surgery, and the Riley Children's Hospital, Indiana University School of Medicine, Indianapolis, 46202, IN, USA.
Frederick J
FJ
Rescorla
D000818:Animals; D023102:Anoikis / Q000235:genetics*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D002470:Cell Survival / Q000235:genetics; D021982:Cell-Matrix Junctions / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D011956:Receptors, Cell Surface