Tetraspanin CO-029 inhibits colorectal cancer cell movement by deregulating cell-matrix and cell-cell adhesions.
Alterations in tetraspanin CO-029 expression are associated with the progression and metastasis of cancers in the digestive system. However, how CO-029 promotes cancer metastasis is still poorly understood. To determine the mechanism, we silenced CO-029 expression in HT29 colon cancer cells and found that the CO-029 knockdown significantly reduced cell migratory ability. The diminished cell migration was accompanied by the upregulation of both integrin-dependent cell-matrix adhesion on laminin and calcium-dependent cell-cell adhesion. The cell surface levels of laminin-binding integrin α3β1 and fibronectin-integrin α5β1 were increased while the level of CD44 was decreased upon CO-029 silencing. These changes contribute to the altered cell-matrix adhesion. The deregulated cell-cell adhesion results, at least partially, from increased activity of cadherins and reduced level of MelCAM. In conclusion, CO-029 functions as a regulator of both cell-matrix and cell-cell adhesion. During colon cancer progression, CO-029 promotes cancer cell movement by deregulating cell adhesions.
Vascular Biology and Cancer Centers and Department of Medicine and Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Qiusha
Q
Guo
Bing
B
Xia
Feng
F
Zhang
Mekel M
MM
Richardson
Minghao
M
Li
Julian S
JS
Zhang
Feng
F
Chen
Xin A
XA
Zhang
D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000378:metabolism; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*
D018960:Hyaluronan Receptors; D039201:Integrin alpha3beta1; D039081:Integrin alpha5beta1; D007797:Laminin; C065609:TSPAN8 protein, human; D059470:Tetraspanins