title: Balanced Tiam1-rac1 and RhoA drives proliferation and invasion of pancreatic cancer cells.
abstract: Tiam1 is a rac1-specific guanine nucleotide exchange factor, and Tiam1-rac1 is involved in a number of cellular processes. Rac1 and RhoA act as molecular switches that cycle between GTP- and GDP-bound states to balance the activities of rac1 and RhoA. The downregulation of rac1 activity leads to upregulation of RhoA activity, which promotes invasion and migration of pancreatic cancers cells. At present, however, the role of Tiam1-rac1 and RhoA in pancreatic cancers is not fully understood. We found that Tiam1 was upregulated in pancreatic cancers and was significantly expressed in tumors without lymph node involvement or distant metastasis compared with cancers where there was involvement. Although Tiam1-rac1 signaling promoted pancreatic cancer cell proliferation and tumor growth via the Wnt signaling pathway in vitro and in vivo, inhibiting Tiam1-rac1 signaling did not prolong the overall survival time in vivo. This provided evidence that there was a balance between rac1 and RhoA activities in pancreatic cancers. Furthermore, only the combined inhibition of Tiam1-rac1 and RhoA had a beneficial effect on the growth of pancreatic cancers in vivo. Taken together, these results suggest that the progression of pancreatic tumors is partially controlled by the balance between Tiam1-rac1 and RhoA.
authors: Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, PR China.
authors: Xingjun
authors: X
authors: Guo
authors: Min
authors: M
authors: Wang
authors: Jianxin
authors: J
authors: Jiang
authors: Chengchen
authors: C
authors: Xie
authors: Feng
authors: F
authors: Peng
authors: Xu
authors: X
authors: Li
authors: Rui
authors: R
authors: Tian
authors: Renyi
authors: R
authors: Qin
mesh_terms: D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009361:Neoplasm Invasiveness / Q000235:genetics; D010190:Pancreatic Neoplasms; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D060449:Wnt Signaling Pathway; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C107953:RAC1 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C066737:RHOA protein, human; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein