Upregulation of LGALS1 is associated with oral cancer metastasis

作者：Jimin Li, Chien-Wei Tseng, Chi‐Chen Lin, Ching‐Hsuan Law, Yu‐An Chien, Wen‐Hung Kuo, Hsiu‐Chuan Chou, Wen‐Ching Wang, Hong‐Lin Chan · 发表于：Therapeutic Advances in Medical Oncology · 年份：2018 · DOI：10.1177/1758835918794622 · 被引用次数：39 · 研究领域：Proteoglycans and glycosaminoglycans research、Glycosylation and Glycoproteins Research、Bone and Dental Protein Studies

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, d...