GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression.
GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression.
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GATA4 调节炎症驱动的胰腺导管腺癌进展
DOI：
10.3389/fcell.2021.640391
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yang L
中科院分区：
文献类型：
--
作者：
Jiang W;Chen C;Huang L;Shen J;Yang L
癌症相关炎症是胰腺导管腺癌（PDAC）进展的关键分子特征。GATA 4是一种转录因子，参与几种内胚层和中胚层来源的组织如胰腺的调节和正常发育。然而，目前尚不清楚GATA 4是否参与炎症驱动的胰腺癌发展。在此，我们采用定量逆转录PCR、免疫组化和差异表达分析来研究GATA 4与炎症驱动的PDAC之间的关联。我们发现胰腺肿瘤组织中GATA 4的过度表达伴随着炎症巨噬细胞水平的增加。我们使用巨噬细胞条件培养基来验证不同浓度脂多糖治疗后的炎症模型，并确定GATA 4依赖性炎症刺激是否影响胰腺癌细胞的体外侵袭和生长。采用二丁基氯化锡诱导的慢性胰腺炎原位肿瘤异种移植裸鼠模型，评价炎症微环境对体内GATA 4表达的影响。我们的研究结果表明，GATA 4的过表达通过NF-κB和STAT 3信号转导显著加剧了炎症刺激诱导的胰腺癌细胞的侵袭和生长，而GATA 4的沉默减弱了侵袭和生长。总的来说，我们的研究结果表明，炎症驱动的癌症进展依赖于GATA 4的表达，并通过STAT 3和NF-κB信号通路介导。
Cancer-associated inflammation is a key molecular feature in the progression of pancreatic ductal adenocarcinoma (PDAC). GATA4 is a transcription factor that participates in the regulation and normal development of several endoderm- and mesoderm-derived tissues such as the pancreas. However, it remains unclear whether GATA4 is involved in the inflammation-driven development of pancreatic cancer. Here, we employed quantitative reverse transcription PCR, immunohistochemistry, and differential expression analysis to investigate the association between GATA4 and inflammation-driven PDAC. We found that overexpression of GATA4 in pancreatic tumor tissue was accompanied by increased levels of inflammatory macrophages. We used macrophage-conditioned medium to validate inflammation models following treatment with varying concentrations of lipopolysaccharide and determined whether GATA4-dependent inflammatory stimuli affected pancreatic cancer cell invasion and growth in vitro. Nude mouse models of dibutyltin dichloride-induced chronic pancreatitis with orthotopic tumor xenografts were used to evaluate the effect of the inflammatory microenvironment on GATA4 expression in vivo. Our findings indicate that overexpression of GATA4 dramatically aggravated inflammatory stimuli-induced pancreatic cancer cell invasion and growth via NF-κB and STAT3 signaling, whereas silencing of GATA4 attenuated invasion and growth. Overall, our findings suggest that inflammation-driven cancer progression is dependent on GATA4 expression and is mediated through the STAT3 and NF-κB signaling pathways.
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炎症诱发的癌症中的炎症小体。
影响因子：
7.3
作者：
Lin C;Zhang J
通讯作者：
Zhang J
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
3.2
作者：
Denley, Simon M.;Jamieson, Nigel B.;McKay, Colin J.
通讯作者：
McKay, Colin J.
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J
影响因子：
4.6
作者：
Gong J;Muñoz AR;Pingali S;Payton-Stewart F;Chan DE;Freeman JW;Ghosh R;Kumar AP
通讯作者：
Kumar AP