The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer.
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer.
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EGFR-HSF1轴加速胰腺癌的肿瘤发生
DOI：
10.1186/s13046-020-01823-4
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发表时间：
2021-01-09
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Qian W;Chen K;Qin T;Xiao Y;Li J;Yue Y;Zhou C;Ma J;Duan W;Lei J;Han L;Li L;Shen X;Wu Z;Ma Q;Wang Z
背景胰腺导管腺癌（pancreatic ductal adenocarcinoma，PDAC）是一种无症状的恶性肿瘤。我们以前发现热休克因子1（HSF 1）是PDAC进展的关键，本研究的目的是阐明HSF 1的早期激活机制及其在胰腺癌发生中的作用。本研究主要采用胰腺腺泡细胞三维培养和自发性胰腺癌前病变小鼠模型LSL-KrasG 12 D/+; Pdx 1-Cre（KC）（及KC小鼠胰腺炎模型），探讨HSF 1在体内外的促肿瘤发生机制。本研究采用生物信息学和分子生物学方法，探讨HSF 1与表皮生长因子受体（epidermal growth factor receptor，EGFR）的相互作用机制。结果本研究发现，药物抑制HSF 1可以延缓胰腺癌的发生，抑制胰腺炎诱导的胰腺癌前病变的形成。接下来，生物信息学分析揭示了HSF 1和EGFR通路之间的密切联系，我们也证实了它们在胰腺癌前病变中的平行激活。此外，EGFR的药理学抑制抑制胰腺癌的发生和体内HSF 1的活化。事实上，我们证明，EGFR激活介导的胰腺癌肿瘤的发生是部分HSF 1依赖的vitro.ConclusionHence，我们得出结论，EGFR-HSF 1轴促进胰腺癌的启动。
BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.MethodsThe expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model calledLSL-KrasG12D/+; Pdx1-Cre(KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR).ResultsIn this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.ConclusionHence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
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二甲双胍抑制胰腺癌基因小鼠模型中的癌症发生和进展
影响因子：
37.3
作者：
Chen K;Qian W;Jiang Z;Cheng L;Li J;Sun L;Zhou C;Gao L;Lei M;Yan B;Cao J;Duan W;Ma Q
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影响因子：
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通讯作者：
Mulvihill SJ
影响因子：
5
作者：
Lee, KM;Yasuda, H;Ouellette, MM
通讯作者：
Ouellette, MM
DOI：
10.1038/nrm.2017.73
发表时间：
2018-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Gomez-Pastor R;Burchfiel ET;Thiele DJ
通讯作者：
Thiele DJ
影响因子：
2.5
作者：
Giri B;Sethi V;Modi S;Garg B;Banerjee S;Saluja A;Dudeja V
通讯作者：
Dudeja V