Apelin13/APJ promotes proliferation of colon carcinoma by activating Notch3 signaling pathway
| Autor: | Kai Zhang, Tong Chen, Guang-Meng Xu, Ying Liu, Si-Bo Huo, Tong-Jun Liu, Yan Zhou, Ning Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
JAG1 Colorectal cancer business.industry Notch3 Notch signaling pathway Cancer Apelin/APJ colon carcinoma medicine.disease Apelin Metastasis cancer proliferation 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Cancer research medicine Gene silencing Autocrine signalling business neoplasms Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.21904 |
| Popis: | // Tong Chen 1 , Ning Liu 3 , Guang-Meng Xu 2 , Tong-Jun Liu 2 , Ying Liu 2 , Yan Zhou 2 , Si-Bo Huo 2 and Kai Zhang 2 1 Gastrointestinal Surgery Department, The China-Japan Union Hospital of Jilin University, Jilin, China 2 Colorectal Surgery Department, The Second Hospital of Jilin University, Jilin, China 3 General Surgery Department, The First Hospital of Jilin Province Academy of Traditional Chinese Medicine, Jilin, China Correspondence to: Kai Zhang, email: kzchina9710@yahoo.com Keywords: Apelin/APJ, Notch3, colon carcinoma, cancer proliferation Received: July 26, 2017 Accepted: August 23, 2017 Published: October 13, 2017 ABSTRACT Background: The link between Apelin (APL)/APL receptor (APJ) and Jagged (JAG)/Notch signaling pathways in colorectal cancer (CRC) has been poorly investigated. APL/APJ system, a potent angiogenic factor, is up-regulated in a variety of cancers. It contributes to tumor angiogenesis, and correlates with progression of malignancy. JAG/Notch signaling also contributes to progression, proliferation and metastasis of multiple cancers, including CRC. Here we tested the hypothesis that APL/APJ system promotes CRC proliferation by up-regulating Notch3, thus allowing further binding of JAG1 to Notch3. Materials and Methods : We used a variety of methods including Western blot, RT-qPCR, gene silencing, ELISA, immunofluorescence staining, to investigate the interaction between APL/APJ system and Notch3 signaling pathway in both surgically-resected specimens and CRC cell line LS180. Results: We show that the expression of APL13, APJ, and Notch3 is elevated in CRC. We further demonstrate that APL13 can be secreted into culture media of LS180 cells, suggesting the existence of autocrine loop in CRC. Moreover, we found that APL13 stimulated expression of Notch3. Finally, we found that inhibition of either APJ or Notch3 prevents proliferation of LS180 cells. Conclusions: Our results suggest that APL13/APJ and JAG1/Notch3 signaling pathways are linked in CRC. These findings provide a new direction to the efforts targeting effective therapeutic and management approaches in the treatment of CRC. |
| Databáze: | OpenAIRE |
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