Browsing by Author "Hung, Amos C."

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Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation
(2016-09-01)
Hung, Amos C.
;
Lo, Steven
;
Hou, Ming-Feng
;
Lee, Yi-Chen
;
Tsai, Chun-Hao
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. (C) 2016 AACR.
Identification of Id1 as a downstream effector for arsenic-promoted angiogenesis via PI3K/Akt, NF-kappa B and NOS signaling
(2016-01-01)
Tsai, Chun-Hao
;
Yang, Ming-Hui
;
Hung, Amos C.
;
Wu, Shou-Cheng
;
Chiu, Wen-Chin
Exposure to arsenic is known to be a risk factor for various types of cancer. Apart from its carcinogenic activity, arsenic also shows promoting effects on angiogenesis, a crucial process for tumor growth. Yet, the mechanism underlying arsenic-induced angiogenesis is not fully understood. In this study, we aimed at investigating the involvement of inhibitor of DNA binding 1 (Id1) and the associated signal molecules in the arsenic-mediated angiogenesis. Our initial screening revealed that treatment with low concentrations of arsenic (0.5-1 mu M) led to multiple cellular responses, including enhanced endothelial cell viability and angiogenic activity as well as increased protein expression of Id1. The arsenic-induced angiogenesis was suppressed in the Id1-knocked down cells compared to that in control cells. Furthermore, arsenic-induced Id1 expression and angiogenic activity were regulated by PI3K/Akt, NF-kappa B, and nitric oxide synthase (NOS) signaling. In summary, our current data demonstrate for the first time that Id1 mediates the arsenic-promoted angiogenesis, and Id1 may be regarded as an antiangiogenesis target for treatment of arsenic-associated cancer.