C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation

Oncogene
Chenhui ZhaoYongqian Shu

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo. Our results found that the expression of KLF5, GCN5, GDF15, C5aR, and C5a was significantly upregulated in NSCLC patients. Mechanistic exploration in vitro revealed that C5a could facilitate A549 cell proliferation through increasing KLF5, GCN5, and GDF15 expression. Besides, KLF5 and GCN5 could form a complex, binding to GDF15 promoter in a KLF5-dependent manner and leading to GDF15 gene transcription. More importantly, GCN5-mediated KLF5 acetylation contributing to GDF15 gene transcription and cell proliferation upon C5a stimulation, the region (-103 to +58 nt) of GDF15 promoter which KLF5 could bind to...Continue Reading

References

Dec 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Niels C RiedemannPeter A Ward
May 1, 2004·Surgery·Tsukasa TakabayashiJeffrey A Gelfand
Apr 14, 2005·Molecular Cancer Therapeutics·Seungwon KimJeffrey N Myers
Sep 30, 2008·Nature Immunology·Maciej M MarkiewskiJohn D Lambris
May 19, 2009·Cellular and Molecular Life Sciences : CMLS·Jin-Tang Dong, Ceshi Chen
Aug 6, 2009·Cancer Research·Maciej M Markiewski, John D Lambris
Nov 1, 2011·Cell·K G GuruharshaSpyros Artavanis-Tsakonas
Oct 3, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Leticia CorralesRuben Pio
Dec 18, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jing ZhangYingwei Wang
Jan 10, 2014·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Qi LiLi-Wei Wang
Apr 9, 2014·Cancer Medicine·Eli T SayeghAndrew T Parsa
May 2, 2014·Cancer Research·Francesca BruzzeseMartin Augsten
Jul 23, 2014·Oncology Reports·Hidetoshi NittaTakahisa Imamura
Mar 3, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Naoki UrakawaHiroshi Yokozaki
Sep 18, 2015·International Journal of Molecular Sciences·Kun LiuTianhai Ji
Oct 28, 2016·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Takahisa ImamuraHirotaka Iwase
Dec 22, 2015·Immunobiology·Srinivas MamidiMichael Kirschfink
Jan 26, 2016·Pharmacology & Therapeutics·Stephanie KaypeeTapas K Kundu
May 27, 2016·The Journal of Biological Chemistry·Laurence D TownerB Paul Morgan
Mar 2, 2017·The Journal of Clinical Investigation·Vahid Afshar-Kharghan
Jun 4, 2017·Biochemical and Biophysical Research Communications·Kota NoritsuguMinoru Yoshida
Oct 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Meng HouYue Teng

❮ Previous
Next ❯

Citations

Nov 1, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
Apr 6, 2019·Current Pharmaceutical Design·Lei FangChundong Gu
Apr 10, 2019·International Journal of Cancer. Journal International Du Cancer·Yezhong WangZhongmin Yuan
Apr 21, 2020·Endocrine Reviews·Samuel M LockhartStephen O'Rahilly
Apr 20, 2019·Frontiers in Immunology·Daniel AjonaFernando Lecanda
Dec 25, 2019·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Apr 30, 2019·Frontiers in Immunology·Ruben PioJohn D Lambris
Oct 31, 2020·Frontiers in Oncology·Gang DongShiyao Chen
Apr 19, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Luc RochetteCatherine Vergely
Dec 17, 2020·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Apr 4, 2021·Cancer Science·Yao Luo, Ceshi Chen
Jun 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Longfei LiuYingwei Wang
Dec 22, 2021·DNA and Cell Biology·Shuo YangHong Li

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
xenograft
RNA-seq
PCR
ELISA
transfection
ChIP
immunoprecipitation
pulldown
xenografts

Software Mentioned

JASPAR
PASS

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.