title: Silencing of ST6Gal I enhances colorectal cancer metastasis by down-regulating KAI1 via exosome-mediated exportation and thereby rescues integrin signaling.
abstract: Aberrant sialylation has long been correlated with human cancer. Increased ST6 Gal I (β-galactoside α 2, 6 sialyltransferase) and consequently higher levels of cell-surface α 2, 6 sialylation has been associated with human colorectal cancer (CRC) metastasis. We have extensive circumstantial data that sialylation is connected to cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in cancer metastasis. To investigate the molecular mechanism underlying the ST6Gal I-mediated metastasis of CRC, we silenced the ST6Gal I gene in a metastatic SW620 CRC cell line (SW620-shST6Gal I) and examined the metastatic behavior of the cells. We found that various hallmarks of metastatic ability were considerably enhanced in ST6Gal 1-depleted SW620 clones, as assessed both in vitro and in vivo . In particular, the metastasis suppressor, KAI1, was down-regulated in ST6Gal I-deficient SW620 clones. This reflected the increased exosome-mediated exportation of KAI1, and was associated with a decrease in the KAI1-mediated inhibition of integrin. These findings indicate that gene silencing of ST6Gal I could enhance metastasis of CRC by down-regulating KAI1 activity and rescuing its negative effects on integrin signaling.
authors: Yu Ri
authors: YR
authors: Jung
authors: Department of Biochemistry and Medical Research Center , College of Medicine , Chungbuk National University , Cheongju 28644 , Republic of Korea.
authors: Jung-Jin
authors: JJ
authors: Park
authors: National Primate Research Center , Korea Research Institute of Bioscience and Biotechnology , Cheongju 28116 , Republic of Korea.
authors: Yeung Bae
authors: YB
authors: Jin
authors: Department of Radiation Oncology , Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center for Cancer and Tianjin Key laboratory of Cancer Prevention and Therapy , Huan-Hu-Xi Road , Ti-Yuan-Bei , He Xi District , Tianjin 300060 , P.R. China and.
authors: Yuan Jie
authors: YJ
authors: Cao
authors: Division of Radiation Cancer Research , Korea Institute of Radiological and Medical Sciences , Seoul 01812 , Republic of Korea.
authors: Myung-Jin
authors: MJ
authors: Park
authors: Eun Ju
authors: EJ
authors: Kim
authors: Minyoung
authors: M
authors: Lee