Acta Pharmacologica Sinica (2009) 30: 1039-1045; doi: 10.1038/aps.2009.84

Acta Pharmacologica Sinica (2009) 30: 1039-1045; doi: 10.1038/aps.2009.84; published online 1 June 2009

Original Article

α2,6-hyposialylation of c-Met abolishes cell motility of ST6Gal-I-knockdown HCT116 cells

Jin QIAN¹, Cai-hua ZHU¹, Shuai TANG², Ai-jun SHEN¹, Jing AI², Jing LI², Mei-yu GENG^1,2,*, Jian DING^1,*

¹Division of Anti-tumor Pharmacology, Shanghai Institute of Materia Medica, Shanghai 201203, China;²Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China, Qingdao 266003, China

Aim: We aimed to investigate the potential modification of previously unrecognized surface glycoprotein(s) by α2,6-sialylation other than by integrins.

Methods: The expression of β-galactoside α2,6-sialyltransferase (ST 6Gal -I) in the colon cancer cell line HCT116 was reduced by siRNA. The adhesion and Boyden chamber assay were used to detect the variation in cell motility. α2,6-Sialylation proteins were detected with lectin affinity assay. The mRNA expression, protein expression and downstream signaling modulation with siRNA were detected using reverse transcription-polymerase chain reaction, flow cytometry analysis, and Western blot.

Results: In HCT116 cells, the knockdown of ST 6Gal -I inhibited cell motility, but did not affect cell adhesion. This selectively altered cell migration was caused by the loss of α2,6-sialic acid structures on c-Met. Moreover, STAT3 was dephosphorylated at tyrosine 705 in ST 6Gal -I-knockdown (ST 6Gal -I-KD) HCT116 cells.

Conclusion: c-Met is the substrate of ST 6Gal -I. The hyposialylation of c-Met can abolish cell motility in ST 6Gal -I-KD HCT116 cells.

Keywords: cell motility; c-Met; hyposialylation; ST 6Gal ‑I

This work was supported by the National Basic Research Program Grant (No 2003CB716400) of China , the Natural Science Foundation of China for Distinguished Young Scholars (No 30725046) and the Natural Science Foundation of China for Innovation Research Group (No 30721005).

* To whom correspondence should be addressed.
Email gengmy@ouc.edu.cn; suozhang@mail.shcnc.ac.cn
Received 2009-04-10 Accepted 2009-05-04

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