Spinophilin in human cancer–molecular mechanisms and clinical relevance

Abstract

Spinophilin, a multifunctional intracellular protein, has attracted attention within the last years as a novel putative tumor suppressor protein. Recent studies have shown a reduction of spinophilin expression levels in various types of cancer, such as lung adenocarcinoma, ovarian cancer, and chronic myelogenous leukemia. Low expression of spinophilin was also associated with a higher malignant grade in some of these studies. Our own studies on hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC), colorectal adenocarcinoma (CRC) and breast cancer explored the possible role of spinophilin as a proliferative trigger and potentially prognostic factor. We determined the spinophilin expression through immunohistochemistry, quantitative reverse transcriptase-PCR analysis, and used small interfering RNA (siRNA) or stably expressed shRNAs to disable spinophilin in order to investigate the cellular and molecular effects of reduced spinophilin expression. Statistical methods on appropriate cohorts were used to define the prognostic value and impact on clinical outcome of spinophilin expression levels in patients with HCC, HNSCC, or CRC and breast cancer. Spinophilin seems to play an important role as a crucial protein in cell cycle and proliferation, and thus our findings seems to prove this hypothesis derived from other types of cancer. In the cohorts studied, low expression of spinophilin was identified as an independent prognostic factor that indicates poor clinical outcome. In the past, various key molecules and molecular mechanisms highly impacted clinical practice and specific cancer treatment; therefore, novel factors are needed to improve the moderate survival rates of patients with HCC, HNSCC, and CRC. Taken together, spinophilin is a promising new pathophysiological factor and might be a useful novel biomarker for prognostic purposes.