Abstract
Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562. The results of phospho-kinase array analysis showed that SPARC treatment increased phosphorylation of some molecules including protein kinase B (PKB/AKT), ribosomal S6 kinase (RSK), and extracellular signal–regulated kinases (ERK). The expression of SPARC-induced EMT regulator Slug was suppressed by AKT inhibitor, but not ERK and RSK inhibitors. The SPARC expression in grade IV tumor samples is higher when compared to that in grade I–III tumor samples. Our results suggest that SPARC treatment enhances the EMT signaling pathway via activation of AKT, and exogenous SPARC and tumor expressing SPARC might be associated with tumor progression in head and neck cancers.
Highlights
Head and neck cancer is one of most common cancer types worldwide and every year an estimated 49,000 people are newly-diagnosed in United States [1]
The results suggest that treatment induced the mesenchymal phenotype in 100 ng Secreted Protein Acidic and Rich in Cysteine (SPARC) treatment
The results suggest that SPARC treatment induced the mesenchymal phenotype in Detroit 562 cells
Summary
Head and neck cancer is one of most common cancer types worldwide and every year an estimated 49,000 people are newly-diagnosed in United States [1]. SPARCprotein is secreted types of cancer and tumor-associated stroma cells, and matricellular familyfrom whichmany regulates cell-matrix interactions and signaling pathways in cells [8].is considered to regulate cell growth andand metastasis [9]. SPARC reported is secreted from tumor many types of cancer tumor-associated stroma cells, of and is considered previous studies different. SPARC promotes bone metastasis and EMT properties in highly-metastatic low expression in cancer tissue is associated with good prognosis in patients with lung including triple-negative breast cancer, melanoma, and prostate cancers [10,11]. Stromal cancer cells-expressing evidence might suggest stromal is a factorpancreatic to induce tumor mediates invasiveness and metastatic capacity cancerprogression. SPARC have phenotypes and signaling pathways in head and neck cancer cell lines were investigated and the not been fully understood in head and neck cancers. Signaling in head and neck cancer cell lines were investigated and the expression of
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