Upregulation of LGALS1 is associated with oral cancer metastasis

• Published in: Therapeutic advances in medical oncology Vol. 10; p. 1758835918794622
• Main Authors: Li, Ji-Min, Tseng, Chien-Wei, Lin, Chi-Chen, Law, Ching-Hsuan, Chien, Yu-An, Kuo, Wen-Hung, Chou, Hsiu-Chuan, Wang, Wen-Ching, Chan, Hong-Lin
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2018; Sage Publications Ltd; SAGE Publishing
• Subjects: Cell adhesion & migration; Cell migration; Gelatinase B; Invasiveness; Kinases; Lung cancer; Lymph nodes; MAP kinase; Mesenchyme; Metastases; Metastasis; Oral cancer; Original Research; Phenotypes; Phosphorylation; Protein kinase; siRNA; Wound healing; secretomics; LGALS1; metastasis; p38 MAPK; oral cancer
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/1758835918794622

Background: Oral cancer metastasis is a devastating process that contributes to poor prognosis and high mortality, yet its detailed underlying mechanisms remain unclear. Here, we aimed to evaluate metastasis-specific markers in oral cancer and to provide comprehensive recognition concerning functional roles of the specific target in oral cancer metastasis. Methods: Lectin, galactoside-binding, soluble, 1 (LGALS1) was identified by secretomic analysis. LGALS1 expression of patient samples with oral cancer on the tissue microarray were examined by immunochemical (IHC) staining. Small interfering RNA (siRNA)-mediated knockdown of LGALS1 revealed the role of LGALS1 in oral cancer metastasis in vitro and in vivo. Results: LGALS1 was observed to be upregulated in highly invasive oral cancer cells, and elevated LGALS1 expression was correlated with cancer progression and lymph node metastasis in oral cancer tissue specimens. Functionally, silencing LGALS1 resulted in suppressed cell growth, wound healing, cell migration, and cell invasion in oral cancer cells in vitro. Knockdown of LGALS1 in highly invasive oral cancer cells dramatically inhibited lung metastasis in an in vivo mouse model. Mechanistic studies suggested p38 mitogen-activated protein kinase (MAPK) phosphorylation, upregulated MMP-9, and mesenchymal phenotypes of epithelial-mesenchymal transition (EMT) in highly invasive oral cancer cells, whereas siRNA against LGALS1 resulted in the inactivation of p38 MAPK pathway, downregulated MMP-9, and EMT inhibition. Conclusions: These findings demonstrate that elevated LGALS1 is strongly correlated with oral cancer progression and metastasis, and that it could potentially serve as a prognostic biomarker and an innovative target for oral cancer therapy.