1. Academic Validation
  2. ApoC1 promotes the metastasis of clear cell renal cell carcinoma via activation of STAT3

ApoC1 promotes the metastasis of clear cell renal cell carcinoma via activation of STAT3

  • Oncogene. 2020 Sep;39(39):6203-6217. doi: 10.1038/s41388-020-01428-3.
Yang-Ling Li  # 1 Lin-Wen Wu  # 2 3 Ling-Hui Zeng 2 Zuo-Yan Zhang 2 3 Wei Wang 4 Chong Zhang 5 Neng-Ming Lin 6 7
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
  • 2 School of Medicine, Zhejiang University City College, Hangzhou, 310015, Zhejiang, China.
  • 3 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
  • 4 Department of Pathology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
  • 5 School of Medicine, Zhejiang University City College, Hangzhou, 310015, Zhejiang, China. [email protected].
  • 6 Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China. [email protected].
  • 7 Hangzhou Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China. [email protected].
  • # Contributed equally.
Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common renal Cancer and frequently diagnosed at an advanced stage. It is prone to develop unpredictable metastases even with proper treatment. Antiangiogenic therapy is the most effective medical treatment for metastatic ccRCC. Thus, exploration of novel approaches to inhibit angiogenesis and metastasis may potentially lead to a better therapeutic option for ccRCC. Among all the types of Cancer, renal Cancer samples exhibited the maximum upregulation of ApoC1 as referred to in the Oncomine database. The expression of ApoC1 was increased accompanied by ccRCC progression. A high level of ApoC1 was closely related to poor survival time in ccRCC patients. Furthermore, ApoC1 was over-expressed in the highly invasive ccRCC cells as compared to that in the low-invasive ccRCC cells. Besides, ApoC1 promoted metastasis of ccRCC cells via EMT pathway, whereas depletion of ApoC1 alleviated these effects. ApoC1 as a novel pro-metastatic factor facilitates the activation of STAT3 and enhances the metastasis of ccRCC cells. Meanwhile, ApoC1 in the exosomes were transferred from the ccRCC cells to the vascular endothelial cells and promoted metastasis of the ccRCC cells via activating STAT3. Finally, the metastatic potential of the ccRCC cells driven by ApoC1 was suppressed by DPP-4 inhibition. Our study not only identifies a novel ApoC1-STAT3 pathway in ccRCC metastasis but also provides direction for the exploration of novel strategies to predict and treat metastatic ccRCC in the future.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16975
    99.45%, STAT3/5 Inhibitor