REG3A accelerates pancreatic cancer cell growth under IL-6-associated inflammatory condition: Involvement of a REG3A-JAK2/STAT3 positive feedback loop

Cancer Letters
Xiulan LiuMing Xiang

Abstract

Regenerating gene protein (REG) 3A is a 19 kD secretory pancreas protein with pro-growth function. Previously we demonstrated that overexpression of REG3A, acting as a key molecule for up-regulation of the JAK2/STAT3 pathway, contributed to inflammation-related pancreatic cancer (PaC) development. However the exact network associated with REG3A signaling still remains unclear. Here we determined that exposure of human PaC cells to cytokine IL-6 activated the oncogenic JAK2/STAT3 pathway, which directly upregulated REG3A expression, accelerated cell cycle progression by promoting CyclinD1 expression, and enhancing the expression of the anti-apoptosis Bcl family. Importantly, the activation of REG3A would instead enhance the JAK2/STAT3 pathway to constitute a REG3A-JAK2/STAT3 positive feedback loop, which leads to the amplification of the oncogenic effects of IL-6/JAK2/STAT3, a classic pathway linking to inflammation-related tumorigenesis, ultimately resulting in PaC cell over-proliferation and tumor formation both in vitro and in vivo. Moreover, EGFR was found to mediate the REG3A signal for PaC cell growth and JAK2/STAT3 activation, thus functioning as a REG3A receptor. Collectively, our results provide the first evidence for t...Continue Reading

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Citations

Nov 22, 2015·Expert Opinion on Therapeutic Targets·Shin Takasawa
Dec 20, 2015·Molecular and Cellular Endocrinology·Lu-Ting YuChen Luo
Apr 23, 2016·Biochimica Et Biophysica Acta·ShaoPeng WangQuan Zou
Oct 30, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ming XiangYonghui Zhang
Oct 2, 2019·Experimental and Therapeutic Medicine·Mengya ZhangJun Wang
Jun 29, 2017·Cellular and Molecular Life Sciences : CMLS·Jérémy NigriRichard Tomasini
Jan 11, 2020·Frontiers in Oncology·Meng-Ya ZhangJie Guo
Nov 7, 2019·Frontiers in Cell and Developmental Biology·Zijing ChenEmmanuel S Tzanakakis
Aug 28, 2020·Cellular & Molecular Biology Letters·Shuhei Yamada
Mar 20, 2016·Cancer Research·Celine LoncleJuan L Iovanna
Jan 12, 2021·International Reviews of Immunology·Yuwen CaoZhaoliang Su
Jan 23, 2021·Proceedings of the National Academy of Sciences of the United States of America·Kazuhiro MurakamiNick Barker
May 6, 2021·International Journal of Molecular Sciences·Susmita BarmanPunita Dhawan
May 18, 2021·Frontiers in Cell and Developmental Biology·Wojciech J SzlachcicMalgorzata Borowiak
Nov 24, 2021·Molecular Biology Reports·Liying WangFengyuan Che

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