Abstract
BackgroundThe 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 MethodsWe 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Apelin (APL) signaling pathway was recently shown to participate in many physiological and pathophysiological processes [1]
We show that the expression of APL13, apelin receptor (APJ), and Notch3 is elevated in colorectal cancer (CRC)
Our results suggest that APL13/APJ and JAG1/Notch3 signaling pathways are linked in CRC
Summary
Apelin (APL) signaling pathway was recently shown to participate in many physiological and pathophysiological processes [1]. The well-documented roles of APL signaling are closely related to the expression of APJ in hypothalamus, blood vessels, and heart. During blood vessel formation, the level of APJ mRNA in endothelial cells is very high [4, 5] This endothelial expression is associated with the mitogenic action of apelin on these cells, which is necessary for the spread of vascular network. 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 contributes to progression, proliferation and metastasis of multiple cancers, including CRC. We tested the hypothesis that APL/APJ system promotes CRC proliferation by up-regulating Notch, allowing further binding of JAG1 to Notch
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