Hiroki Hashida1,2, Robert J Coffey1. 1. Department of Medicine and Cell Biology, Vanderbilt University Medical Center, Nashville, TN, USA. 2. Department of Surgical Oncology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Abstract
Background: The S100 proteins are characterized by two distinct EF-hand calcium-binding motifs. Several members of the S100 family are involved in cancer progression. S100A14, a member of the S100 family, has been cloned and reported in colon-specific microarray databases. In this study, we assessed the biological and functional significance of S100A14 in normal colon and in colon cancer. Methods: The expression of S100A14 in normal colon and colon cancer was assessed. We used in situ hybridization, reverse transcription polymerase chain reaction (RT-PCR), cell migration assay, cell growth assay, western blotting, and immunohistochemical analysis. Clinicopathological examinations were also performed. Results: S100A14 is expressed in normal colon epithelium and several colon cancer cell lines. However, it is not expressed in SW480 cells. S100A14-overexpressing SW480 cells were established by stable transfection. Interestingly, a decrease in cell motility was observed, as determined using two independent migration assays. S100A14-overexpressing SW480 cells showed increased E-cadherin levels but decreased ability to form colonies in soft agar. Moreover, S100A14 expression was decreased in 95 of 154 human colon cancers, and lower S100A14 expression led to worse prognoses. Conclusions: Our results suggest that S100A14 is involved in cell motility, adhesion, and growth changes in colon cancer and that its expression is inversely correlated with colon cancer progression. S100A14 expression in colon cancer is a useful prognostic marker. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Background: The S100 proteins are characterized by two distinct EF-hand calcium-binding motifs. Several members of the S100 family are involved in cancer progression. S100A14, a member of the S100 family, has been cloned and reported in colon-specific microarray databases. In this study, we assessed the biological and functional significance of S100A14 in normal colon and in colon cancer. Methods: The expression of S100A14 in normal colon and colon cancer was assessed. We used in situ hybridization, reverse transcription polymerase chain reaction (RT-PCR), cell migration assay, cell growth assay, western blotting, and immunohistochemical analysis. Clinicopathological examinations were also performed. Results: S100A14 is expressed in normal colon epithelium and several colon cancer cell lines. However, it is not expressed in SW480 cells. S100A14-overexpressing SW480 cells were established by stable transfection. Interestingly, a decrease in cell motility was observed, as determined using two independent migration assays. S100A14-overexpressing SW480 cells showed increased E-cadherin levels but decreased ability to form colonies in soft agar. Moreover, S100A14 expression was decreased in 95 of 154 human colon cancers, and lower S100A14 expression led to worse prognoses. Conclusions: Our results suggest that S100A14 is involved in cell motility, adhesion, and growth changes in colon cancer and that its expression is inversely correlated with colon cancer progression. S100A14 expression in colon cancer is a useful prognostic marker. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Entities:
Keywords:
S100 family; S100A14; calcium-binding protein; cell motility; colon cancer
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