title: Gab2 facilitates epithelial-to-mesenchymal transition via the MEK/ERK/MMP signaling in colorectal cancer.
abstract: BACKGROUND
  Grb2-associated binder 2 (Gab2), a scaffolding adaptor protein, has recently been implicated in cancer progression. However, the role of Gab2 in the progression and metastasis of colorectal cancer (CRC) remains unclear.
  
  
  METHODS
  Gab2 expression was assessed in CRC patient specimens as well as in CRC cell lines. Recombinant lentivirus vector containing Gab2 gene and its small interfering RNAs were constructed and introduced into CRC cells. Cell migration and invasion ability were evaluated by transwell assays in vitro, and in vivo metastasis was performed on nude mice model. Moreover, the expression of Gab2 and epithelial-to-mesenchymal transition (EMT)-associated proteins (E-cadherin and vimentin) were assessed by western blot and qRT-PCR in CRC cells to evaluate the correlation between Gab2 and EMT. Finally, we evaluated the impact of Gab2 on the activation of its downstream signaling effectors, and furthermore the effects of these pathways on Gab2 induced-EMT were also detected.
  
  
  RESULTS
  We confirmed that increased Gab2 expression correlated with higher tumor node metastasis stage and highly invasive CRC cell lines. Ectopic expression of Gab2 promoted metastasis of CRC cells, whereas silencing of Gab2 resulted in inhibited metastasis both in vitro and in vivo. Overexpression of Gab2 in CRC cells induced EMT, whereas knockdown of Gab2 had the opposite effect. Furthermore, upregulation of Gab2 expression obviously stimulated the activation of extracellular signal-regulated kinase-1/2 (ERK1/2), and increased the expression of matrix metalloproteinase-7 (MMP7) and matrix metalloproteinase-9 (MMP9) in CRC cells. Conversely, downregulation of Gab2 expression significantly decreased the activation of ERK1/2, and inhibited MMP7 and MMP9 expression. U0126, an inhibitor of mitogen-activated protein kinase (MEK), can reverse the effects of Gab2 on EMT.
  
  
  CONCLUSIONS
  Our work highlights that Gab2 induces EMT through the MEK/ERK/MMP pathway, which in turn promotes intestinal tumor metastasis.
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. dcb06296632@163.com.
authors.forename: Chenbo
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. luojm128@163.com.
authors.forename: Junmin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. ljlk6863@163.com.
authors.forename: Longmei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. lss2958@126.com.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. YLW880307@163.com.
authors.forename: Liwen
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. 929856167@qq.com.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. 1069910634@qq.com.
authors.forename: Qianyi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Zunyi Medical College, Zunyi, 563003, PR China. qinhuan0425@aliyun.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Immunology, Zunyi Medical College, Immunology Innovation Base of Postgraduate Education in Guizhou Province, Zunyi, 563003, PR China. 394918697@qq.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Zunyi Medical College, Zunyi, 563003, PR China. jh_f@163.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Feng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D045726:Metalloproteases / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D045726:Metalloproteases