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.
Highlights
Breast cancer is the most commonly diagnosed type of cancer and the second most fatal cancer of women in the world [1]
To identify factors that are associated with metastasis, we selected an aggressive breast cancer cell line MDA-MB231 and a non-aggressive cell line MCF-7
Using RT-PCR, we analyzed the expression of growth factors, oncogenes and factors that may be related to tumor metastasis
Summary
Breast cancer is the most commonly diagnosed type of cancer and the second most fatal cancer of women in the world [1]. Over the last few decades, various targeted therapeutics have been introduced into the clinic, but there has been no corresponding improvement in patient survival, primarily because of the malignant behavior of breast cancer. Metastasis of breast cancer from primary location to distant sites is the main cause contributing to disease fatalities. It is urgent to identify key molecular regulators in metastasis to improve the prognosis assessment and treatment of breast cancer patients. The oncogenic role of FLI1 was first confirmed in mice erytholeukemia [7]. Only recently has FLI1 been reported to show aberrant activation in patients with solid tumors [8]. Despite these advances, little is known about the role of FLI1 in metastasis, in breast cancer
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