Abstract
Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Protein expressions of cofilin, N-WASP, α-parvin, β-parvin, and PINCH1 were examined by immunohistochemistry in 72 human laryngeal squamous cell carcinomas. Correlations with clinicopathological data and survival were evaluated. All proteins examined were overexpressed in human laryngeal carcinomas compared to adjacent nonneoplastic epithelium. High expression of PINCH1 was associated significantly with high grade, lymph node-positive, and advanced stage disease. Moreover, high PINCH1 expression significantly associated with poor overall and disease-free survival and high cytoplasmic PINCH1 expression was shown by multivariate analysis to independently predict poor overall survival. In conclusion, we provide novel evidence that focal adhesion signaling to actin cytoskeleton is implicated in human laryngeal carcinogenesis and PINCH1 has prognostic significance in the disease.
Highlights
Laryngeal cancer is the second most common neoplasm of the upper aerodigestive tract [1]
Actin-binding proteins cofilin and N-WASP and the focal adhesion proteins α- and β-parvin and PINCH are critically involved in the regulation of actin cytoskeleton dynamics and cell adhesion, survival, and migration, and several studies implicate their altered expression in cancer progression [2,3,4,5,6,7,8,9,10,11,12,13,14,15, 21, 22, 24,25,26,27,28,29,30,31]
We originally demonstrate their overexpression in human laryngeal carcinoma and we further show that high expression of PINCH1 is an independent poor prognostic factor
Summary
Laryngeal cancer is the second most common neoplasm of the upper aerodigestive tract [1]. The 5-year survival for laryngeal squamous cell carcinoma is 60%, and despite the progress in the diagnosis and treatment, survival has not improved much over the years [1]. Cell migration is crucial in tumor invasion and metastasis and is regulated through actin cytoskeleton reorganization and focal adhesion turnover. Actin reorganization leads to the formation of protrusive structures at the leading edge of cancer cells that mediate migration and invasion through the extracellular matrix (ECM) [2]. Several studies suggest a significant role of cofilin in cancer cell invasion and metastasis [2, 5, 6]. Increased expression of cofilin has been previously demonstrated in various human cancers including nonsmall cell lung cancer and squamous esophageal carcinoma, and overexpression of cofilin was frequently associated with adverse prognosis and resistance to therapy [7,8,9,10]
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