title: Tiam1 is associated with hepatocellular carcinoma metastasis.
abstract: We have previously demonstrated that overexpression of T lymphoma invasion and metastasis 1 (Tiam1) is correlated with poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we tried to further investigate the potential roles of Tiam1 in the progression of HCC in a larger set of samples. By detecting Tiam1 expression in 213 HCC patients, we observed that Tiam1 had a higher probability of being overexpressed in HCC patients with metastasis than those without metastasis (68.3% vs. 52.7%, p = 0.036). In addition, the cell line with high metastatic potential expressed more Tiam1 than did the cell line with low metastatic potential. Overexpression of Tiam1 was suggested to be significantly correlated with HCC metastasis. We stably upregulated Tiam1 expression in MHCC97L as well as knocked down Tiam1 expression in HCCLM6. We also investigated the effects of Tiam1 overexpression and knockdown on HCC cells proliferation, migration and invasion in vitro and on tumorigenicity and metastasis in vivo. Overexpression of Tiam1 increased proliferation, migration and invasion of MHCC97L cells, while knockdown of Tiam1 in HCCLM6 cells resulted in the reverse. In vivo functional studies showed upregulation of Tiam1 expression led to an enhancement of tumorigenicity and metastatic potential in mice. However, knockdown of Tiam1 expression exhibited nearly 2.2-fold retardation in tumor growth and great inhibition on tumor metastases. Our results indicate that Tiam1, as a metastasis-related gene, may contribute to HCC invasion and metastasis, and consequently, it may be a useful biomarker for therapeutic strategy and control in HCC treatment.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Ye
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Zheng
authors.forename: Laiyu
authors.initials: L
authors.lastname: Liu
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Longhua
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D015854:Up-Regulation
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D012333:RNA, Messenger; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human