LIFR promotes tumor angiogenesis by up-regulating IL-8 levels in colorectal cancer

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Hao-Xuan WuRen Zhao

Abstract

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.

Citations

Oct 1, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xianjie JiangWei Xiong
Dec 13, 2019·Disease Markers·Yaqin BieYunfeng Li
Sep 5, 2019·Frontiers in Cellular Neuroscience·Maxime PenissonFiona Francis
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Marta Rojas-TorresMª Carmen Durán-Ruiz
Jan 29, 2021·Frontiers in Cell and Developmental Biology·Dandan ZhengLiangxing Wang
Aug 22, 2021·Gene·Saiedeh Razi SoofiyaniVahideh Tarhriz
Dec 4, 2021·Frontiers in Immunology·Denis A KleymenovAlexander L Gintsburg

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