Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility

• Type of Material: Article
• Authors: Hui-min Zhou, Sun Yat-sen University; Yuan-yuan Fang, Sun Yat-sen University; Paul M. Weinberger, Georgia Regents University; Ling-ling Ding, Wu Han University; John K. Cowell, Georgia Regents University; Farlyn Z. Hudson, Georgia Regents University; Mingqiang Ren, Georgia Regents University; Jeffrey R. Lee, Georgia Regents University; Qi-kui Chen, Sun Yat-sen University; Hong Su, Sun Yat-sen University; William Dynan, Emory University; Ying Lin, Sun Yat-sen University
• Language: English
• Date: 2016-02-04
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Zhou et al. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12885-016-2105-8
• Title of Journal or Parent Work: BMC Cancer
• ISSN: 1471-2407
• Volume: 16
• Issue: 1
• Grant/Funding Information: Grant [2013] 163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology, and Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes also supported this work.; A National Institutes of Health/National Cancer Institute grant CA95941 (WSD) provided additional support.; The National Natural Science Foundation of China (No. 30901782, YL), the Fundamental Research Funds for the Central Universities (No. 11ykpy32, YL), and the Yat-Sen Scholarship for Young Scientist (YL) supported this work.
• Keywords: Gene regulation; Experimental metastasis; Colorectal cancer; Invasiveness; Biomarker; Transgelin
• Research Categories: Chemistry, Biochemistry; Biology, Genetics; Health Sciences, Oncology

Abstract

Background: Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. Methods: Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. Results: Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. Conclusions: Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.