Galectin-1-Mediated tumor invasion and metastasis, Up-Regulated matrix metalloproteinase expression, and reorganized actin cytoskeletons

Ming Heng Wu, Tse Ming Hong, Hui Wen Cheng, Szu Hua Pan, Yu Ray Liang, Hsiao Chin Hong, Wei Fan Chiang, Tung Yiu Wong, Dar Bin Shieh, Ai Li Shiau, Ying Tai Jin, Yuh Ling Chen

Research output: Contribution to journalArticlepeer-review

130 Citations (Scopus)

Abstract

Galectin-1 (Gal-1) is a β-galactose-binding lectin; its expression level has been reported to correlate with tumor progression, Gal-1 is highly expressed in the invasive front of primary tumors and in the cancer cells of metastatic lesions in the lymph nodes of patients with oral squamous cell carcinoma. However, the molecular mechanism of Gal-1 in tumor metastasis is not completely clear. We found that increased Gal-1 expression is closely associated with its high levels of invasion in lung adenocarcinoma and oral squamous cell carcinoma cell lines. Knocking down Gal-1 with small interfering RNA in highly invasive cancer ceils reduced their invasion levels. Moreover, the invasion ability of poorly invasive cancer cells was significantly increased after Gal-1 overexpression of Gal-1. Mechanism studies revealed that Gal-1 promoted tumor invasion mainly by up-regulating matrix metalloproteinase (MMP)-9 and MMP-2 and by reorganizing actin cytoskeleton. Gal-1 enhanced the activation of Cdc42, a small GTPase and member of the Rho family, thus increasing the number and length of filopodia on tumor cells. Furthermore, Gal-1 -overexpressing cells had higher metastatic abilities in tail vein metastasis assays in vivo. We conclude that Gal-1 is involved in tumor invasion and metastasis by increasing MMP expression and reorganizing cytoskeletons in oral cancers and lung adenocarcinoma.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalMolecular Cancer Research
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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