title: Friend leukemia virus integration 1 activates the Rho GTPase pathway and is associated with metastasis in breast cancer.
abstract: Breast cancer is the most prevalent malignant disease in women worldwide. In patients with breast cancer, metastasis to distant sites directly determines the survival outcome. However, the molecular mechanism underlying metastasis in breast cancer remains to be defined. In this report, we found that Friend leukemia virus integration 1 (FLI1) proto-oncogene was differentially expressed between the aggressive MDA-MB231 and the non-aggressive MCF-7 breast cancer cells. Congruently, immunohistochemical staining of clinical samples revealed that FLI1 was overexpressed in breast cancers as compared with the adjacent tissues. The abundance of FLI1 protein was strongly correlated with the advanced stage, poor differentiation, and lymph node metastasis in breast cancer patients. Knockdown of FLI1 with small interfering RNAs significantly attenuated the potential of migration and invasion in highly metastatic human breast cancer cells. FLI1 oncoprotein activated the Rho GTPase pathway that is known to play a role in tumor metastasis. This study for the first time identifies FLI1 as a clinically and functionally important target gene of metastasis, providing a rationale for developing FLI1 inhibitors in the treatment of breast cancer.
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.|Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Tian
authors.affiliation: Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.|Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Cancer Center, the First Hospital of Jilin University, Changchun, China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C078433:FLI1 protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051789:Proto-Oncogene Protein c-fli-1; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins
keywords: FLI1; RhoA pathway; breast cancer; metastasis; oncogene