Effect of KAI1(CD82) sialylation on the metastatic behavior of human colon cancer cells

다국어 초록 (Multilingual Abstract)

The cell membrane glycoprotein KAI1 (CD82) is a candidate metastasis suppressor gene that has been indicated in the progression of solid tumors. KAI1 is significantly downregulated in various human malignancies. However, the expression and mechanism of regulation of KAI1 in metastasis has not yet been fully elucidated. Previously, it is suggested that N-glycosylation of KAI1 occurred at high level and lead to significant inhibition or promotion of cell motility depending on the extracellular matrix. In particular, little is known about the glycosylation of KAI1 and its functional role in cancer metastasis. Recently, we demonstrated that expression of ST6 Gal I, which was highly expressed in colon cancer, was responsible for integrin 1-mediated adhesion and migration in human colon cancer. Remarkably, KAI1 inhibits the tumor metastasis via interaction with tetraspanins, integrins and chemokines which are responsible for cell migration, adhesion and signalling. We found for the first time that KAI1 was sialylated by ST6 Gal I in human colon cancer cells and sialic acid modification was involved in stabilization of KAI1 by proteasome-dependent manner. Also, abolishment of Asn residues largely disrupts the migration-, invasion-, suppressive activities of KAI1. Importantly, when KAI1 was expressed in HCT116 human colon cancer cells with ST6 Gal I, inhibitory effects on migration and invasion was abrogated by altering of p130CAS-Crk coupling, a signaling step for integrin dependent migration. Moreover, sialylated KAI1 interacted with PKC-integrin and is unlikely to inhibit cell migration through its associated proteins. These new observations may indicated that KAI1 can be stably expressed by sialylation in the process of tumor malignancy and sialylation profoundly affects KAI1, leading to significant alterations of functions as metastasis suppressor.