國家衛生研究院 NHRI:Item 3990099045/11692

NHRI > National Institute of Cancer Research > Wen-Chun Hung > Conference Papers/Meeting Abstract > Item 3990099045/11692

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11692

Title:	c-Myc promotes lymphatic metastasis of pancreatic neuroendocrine tumor through VEGFC upregulation
Authors:	Chang, TM;Shan, YS;Chu, PY;Lin, HY;Huang, KW;Hung, WC;Chen, LT;Tsai, HJ
Contributors:	National Institute of Cancer Research
Abstract:	Lymphangiogenesis is essential for tumor metastasis via lymphatic system. c-Myc overexpression has been found in many cancers and is involved in tumorigenesis. However, whether c-Myc participates in lymphangiogenesis of pancreatic neuroendocrine tumor (pNET) microenvironment is unclear. We have found that high expression of c-Myc was commonly observed in pNETs previously. In this study, we found that VEGFC expression was increased in human and mouse pNET cell lines with c-Myc overexpression. Mechanistically, c-Myc transcriptionally upregulated VEGFC expression through direct binding to E-box of VEGFC promoter and enhanced VEGFR3 phosphorylation and tube formation of lymphatic endothelial cells. In mouse model, mice bearing pNET cells with c-Myc overexpression had more lymph node metastasis. Combine treatment of mTOR inhibitor, RAD001, with c-Myc inhibitor, 10058-F4, or VEGFC neutralizing chimera protein, VEGFR3/Fc, reduced lymph node metastasis of the mice. Taken together, we demonstrated that c-Myc enhances lymph node metastases via upregulating VEGFC/VEGFR3 axis. Simultaneously targeting mTOR and c-Myc or VEGFC may attenuate c-Myc induced lymphangiogenesis of pNET.
Date:	2018-12
Relation:	Cancer Science. 2018 Dec;109(Suppl. 2):866.
Link to:	https://doi.org/10.1111/cas.13904
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000453773604123
Appears in Collections:	[Wen-Chun Hung] Conference Papers/Meeting Abstract [Li-Tzong Chen] Conference Papers/Meeting Abstract [Hui-Jen Tsai] Conference Papers/Meeting Abstract

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