title: New insight into the key proteins and pathways involved in the metastasis of colorectal carcinoma.
abstract: Metastasis-associated genomic alterations have been recognized to play a critical role in tumor metastasis. Primary and metastatic tumor cells in mice and tumors in a patient were studied by cDNA array analysis. Selected genes were determined by RT-PCR and immunohistochemistry. Pathways on changed genes were statistically analyzed. The function of Grb2 was determined by in vitro wound assay. Nodal metastatic cells had a stronger ability of growth and metastasis than primary tumor cells. A total of 376 genes showed a different expression between primary and metastatic cells. The expression of Grb2 and genes in the Grb2-mediated pathways was significantly elevated in the metastases. Elevated levels of Grb2 expression in metastases were related to the distant metastasis of colorectal carcinoma. Blocking the Grb2-SH2 domain signaling transduction inhibited cell motility. Metastasis-associated genes identified by cDNA and tissue microarrays provide potentially valuable information on the metastasis of colorectal tumors. Overexpression of Grb2 may contribute to tumor growth, invasiveness and metastasis.
authors.affiliation: Department of Oncology, Changzheng Hospital, Shanghai, PR China.
authors.forename: Guan-Zhen
authors.initials: GZ
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Ya-Qiu
authors.initials: YQ
authors.lastname: Long
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Mu
authors.forename: Jie-jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018076:DNA, Complementary / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015398:Signal Transduction
chemical_list: D018076:DNA, Complementary; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse