ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer.
ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer.
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DOI：
10.3390/cells10102509
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发表时间：
2021-09-22
期刊：
影响因子：
6
通讯作者：
Takasaki T
中科院分区：
文献类型：
--
作者：
Sugiura R;Satoh R;Takasaki T
RAF/MEK/ERK信号通路调节多种细胞过程，如细胞增殖、分化、运动和存活。ERK 1/2的激活通常促进细胞增殖，其失调的活性是许多癌症的标志。因此，ERK通路的组分和调节剂被认为是癌症的潜在治疗靶点，并且该通路的抑制剂，包括一些MEK和BRAF抑制剂，已经在临床中使用。值得注意的是，ERK 1/2激酶在某些条件下也具有促凋亡功能，并且增强的ERK 1/2信号传导可导致肿瘤细胞死亡。尽管介导ERK活化和凋亡的化合物的库正在扩大，并且各种抗癌化合物在发挥其抗增殖作用的同时诱导ERK活化，但ERK 1/2介导的细胞死亡的潜在机制仍然是模糊的。最近的研究强调了双特异性磷酸酶（DUSPs）在确定ERK在癌症中的促凋亡与抗凋亡功能中的重要性。在这篇综述中，我们将总结最近的主要研究结果，了解ERK在细胞凋亡中的作用，重点是介导ERK依赖性细胞凋亡的主要化合物。进一步确定这些化合物与细胞死亡相关的分子靶点的研究对于利用这些化合物开发有效的癌症治疗方法至关重要。
The RAF/MEK/ERK signaling pathway regulates diverse cellular processes as exemplified by cell proliferation, differentiation, motility, and survival. Activation of ERK1/2 generally promotes cell proliferation, and its deregulated activity is a hallmark of many cancers. Therefore, components and regulators of the ERK pathway are considered potential therapeutic targets for cancer, and inhibitors of this pathway, including some MEK and BRAF inhibitors, are already being used in the clinic. Notably, ERK1/2 kinases also have pro-apoptotic functions under certain conditions and enhanced ERK1/2 signaling can cause tumor cell death. Although the repertoire of the compounds which mediate ERK activation and apoptosis is expanding, and various anti-cancer compounds induce ERK activation while exerting their anti-proliferative effects, the mechanisms underlying ERK1/2-mediated cell death are still vague. Recent studies highlight the importance of dual-specificity phosphatases (DUSPs) in determining the pro- versus anti-apoptotic function of ERK in cancer. In this review, we will summarize the recent major findings in understanding the role of ERK in apoptosis, focusing on the major compounds mediating ERK-dependent apoptosis. Studies that further define the molecular targets of these compounds relevant to cell death will be essential to harnessing these compounds for developing effective cancer treatments.
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影响因子：
11.2
作者：
Bartholomeusz C;Rosen D;Wei C;Kazansky A;Yamasaki F;Takahashi T;Itamochi H;Kondo S;Liu J;Ueno NT
通讯作者：
Ueno NT
影响因子：
3.7
作者：
Arkun Y;Yasemi M
通讯作者：
Yasemi M
影响因子：
4.2
作者：
Baines AT;Xu D;Der CJ
通讯作者：
Der CJ
DOI：
10.1006/bbrc.1998.9256
发表时间：
1998-09-08
影响因子：
3.1
作者：
Bang, YJ;Kwon, JH;Yang, YC
通讯作者：
Yang, YC
影响因子：
5.5
作者：
Casar B;Crespo P
通讯作者：
Crespo P