title: Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.
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.
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.|Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.|Department of Gastroenterology and Hepatology, The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, 510000, China.
authors: Hui-Min
authors: HM
authors: Zhou
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.|Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors: Yuan-Yuan
authors: YY
authors: Fang
authors: Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA, 30912, USA.|GRU Cancer Center, Georgia Regents University, Augusta, GA, USA.
authors: Paul M
authors: PM
authors: Weinberger
authors: Department of Anatomy, Wu Han University, Wuhan, China.
authors: Ling-Ling
authors: LL
authors: Ding
authors: GRU Cancer Center, Georgia Regents University, Augusta, GA, USA.
authors: John K
authors: JK
authors: Cowell
authors: Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA, USA.
authors: Farlyn Z
authors: FZ
authors: Hudson
authors: GRU Cancer Center, Georgia Regents University, Augusta, GA, USA.
authors: Mingqiang
authors: M
authors: Ren
authors: Department of Pathology, Georgia Regents University, and Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA.
authors: Jeffrey R
authors: JR
authors: Lee
authors: Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors: Qi-Kui
authors: QK
authors: Chen
authors: Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors: Hong
authors: H
authors: Su
authors: Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA, USA. wdynan@emory.edu.|Departments of Radiation Oncology and Biochemistry, Emory University, Atlanta, GA, USA. wdynan@emory.edu.
authors: William S
authors: WS
authors: Dynan
authors: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. linwy@mail.sysu.edu.cn.|Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. linwy@mail.sysu.edu.cn.
authors: Ying
authors: Y
authors: Lin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C051615:transgelin