Extracellular visfatin-promoted malignant behavior in breast cancer is mediated through c-Abl and STAT3 activation

Amos C. Hung, Steven Lo, Ming Feng Hou, Yi Chen Lee, Chun Hao Tsai, Yuan Yin Chen, Wangta Liu, Yu Han Su, Yi Hsuan Lo, Chie Hong Wang, Shiou Chen Wu, Ya Ching Hsieh, Stephen Chu Sung Hu, Ming Hong Tai, Yun-Ming Wang, Shyng Shiou F. Yuan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Purpose: Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings. Experimental Design: Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively. Results: Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatinpromoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein-injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib. Conclusions: Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer.

Original languageEnglish
Pages (from-to)4478-4490
Number of pages13
JournalClinical Cancer Research
Issue number17
StatePublished - 1 Sep 2016

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