Research Papers:

Apelin13/APJ promotes proliferation of colon carcinoma by activating Notch3 signaling pathway

Tong Chen, Ning Liu, Guang-Meng Xu, Tong-Jun Liu, Ying Liu, Yan Zhou, Si-Bo Huo and Kai Zhang _

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Oncotarget. 2017; 8:101697-101706. https://doi.org/10.18632/oncotarget.21904

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Tong Chen1, Ning Liu3, Guang-Meng Xu2, Tong-Jun Liu2, Ying Liu2, Yan Zhou2, Si-Bo Huo2 and Kai Zhang2

1Gastrointestinal Surgery Department, The China-Japan Union Hospital of Jilin University, Jilin, China

2Colorectal Surgery Department, The Second Hospital of Jilin University, Jilin, China

3General Surgery Department, The First Hospital of Jilin Province Academy of Traditional Chinese Medicine, Jilin, China

Correspondence to:

Kai Zhang, email: [email protected]

Keywords: Apelin/APJ, Notch3, colon carcinoma, cancer proliferation

Received: July 26, 2017     Accepted: August 23, 2017     Published: October 13, 2017


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.

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