title: AKT and JNK Signaling Pathways Increase the Metastatic Potential of Colorectal Cancer Cells by Altering Transgelin Expression.
abstract: BACKGROUND
  Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in transgelin regulation.
  
  
  OBJECTIVE
  To examine the role of AKT and JNK signaling in transgelin regulation in colorectal cancer progression.
  
  
  METHODS
  Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton.
  
  
  RESULTS
  Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in transgelin downregulation. When transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics.
  
  
  CONCLUSIONS
  This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of transgelin, which potentially contributes to CRC progression and metastasis.
authors.affiliation: Department of Gastroenterology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107. W. Yanjiang Road, Guangzhou, 510120, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107. W. Yanjiang Road, Guangzhou, 510120, People's Republic of China. Dr_chenqikui@163.com.
authors.forename: Qikui
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107. W. Yanjiang Road, Guangzhou, 510120, People's Republic of China. Dr_linying@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008840:Microfilament Proteins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Colorectal cancer; JNK; Metastasis; SM22; Transgelin