Crosstalk between ERK and MRTF‐A signaling regulates TGFβ1‐induced epithelial‐mesenchymal transition
Crosstalk between ERK and MRTF‐A signaling regulates TGFβ1‐induced epithelial‐mesenchymal transition
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ERK 和 MRTF 之间的串扰 —A 信号传导调节 TGFβ1 — 诱导的上皮 — 间质转化
DOI：
10.1002/jcp.30705
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发表时间：
2022
影响因子：
5.6
通讯作者：
Gomez, Esther W.
中科院分区：
文献类型：
--
作者：
Nalluri, Sandeep M.;Sankhe, Chinmay S.;O'Connor, Joseph W.;Blanchard, Paul L.;Khouri, Joelle N.;Phan, Steven H.;Virgi, Gage;Gomez, Esther W.
上皮-间质转化（EMT）是一个生理过程，在胚胎发生和伤口愈合过程中至关重要，也有助于导致纤维化和癌症等病理学。 EMT 的特点是显着的基因表达变化、细胞间接触的丧失、细胞骨架的重塑和运动能力的增强。在 EMT 的后期，细胞可以表现出肌成纤维细胞样特性，间质蛋白标记物 α-平滑肌肌动蛋白的表达增强，收缩活性增强。转化生长因子 (TGF)-β1 是一种众所周知的 EMT 诱导剂，它可激活大量信号级联反应，包括细胞外信号调节激酶 (ERK)。之前的报道已经证明了 ERK 信号在 EMT 早期阶段的作用，但 ERK 信号对 EMT 后期的分子影响仍不清楚。在这里，我们发现抑制 ERK 磷酸化可增强粘着斑、应力纤维形成、细胞收缩性以及与 TGFβ1 诱导的乳腺上皮细胞 EMT 相关的基因表达变化。这些效应部分是由心肌素相关转录因子 A 的磷酸化状态和亚细胞定位介导的。这些发现表明信号级联之间复杂的串扰在调节 EMT 进展中发挥着重要作用，并提出了控制 EMT 过程的新方法。
Epithelial‐mesenchymal transition (EMT) is a physiological process that is essential during embryogenesis and wound healing and also contributes to pathologies including fibrosis and cancer. EMT is characterized by marked gene expression changes, loss of cell–cell contacts, remodeling of the cytoskeleton, and acquisition of enhanced motility. In the late stages of EMT, cells can exhibit myofibroblast‐like properties with enhanced expression of the mesenchymal protein marker α‐smooth muscle actin and contractile activity. Transforming growth factor (TGF)‐β1 is a well‐known inducer of EMT and it activates a plethora of signaling cascades including extracellular signal‐regulated kinase (ERK). Previous reports have demonstrated a role for ERK signaling in the early stages of EMT, but the molecular impacts of ERK signaling on the late stages of EMT are still unknown. Here, we found that inhibition of the phosphorylation of ERK enhances focal adhesions, stress fiber formation, cell contractility, and gene expression changes associated with TGFβ1‐induced EMT in mammary epithelial cells. These effects are mediated in part by the phosphorylation state and subcellular localization of myocardin‐related transcription factor‐A. These findings indicate that the intricate crosstalk between signaling cascades plays an important role in regulating the progression of EMT and suggests new approaches to control EMT processes.
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DOI：
10.1513/pats.200601-004tk
发表时间：
2006-06-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Willis, Brigham C;duBois, Roland M;Borok, Zea
通讯作者：
Borok, Zea
影响因子：
4.8
作者：
Lu, X;Law, BK;Moses, HL
通讯作者：
Moses, HL
影响因子：
3.4
作者：
Dembo, M;Wang, YL
通讯作者：
Wang, YL
DOI：
10.1164/rccm.200903-0322oc
发表时间：
2009-10-01
影响因子：
24.7
作者：
Tanjore, Harikrishna;Xu, Xiaochuan C.;Lawson, William E.
通讯作者：
Lawson, William E.
影响因子：
3.3
作者：
Bhowmick, NA;Ghiassi, M;Moses, HL
通讯作者：
Moses, HL