EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?
EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?
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DOI：
10.3390/cancers13040700
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发表时间：
2021-02-09
期刊：
影响因子：
5.2
通讯作者：
Fazio VM
中科院分区：
文献类型：
--
作者：
Cioce M;Fazio VM
Ephrin受体及其配体通过协调细胞粘附和排斥的复杂程序在器官形成和组织修复中起重要作用，然而，该相同系统在癌症发展中起作用。事实上，EphA 2水平在肿瘤中比正常组织更高，并且在体内和体外治疗后进一步增加。EphA 2的分子状态、其亚细胞定位、配体和源自肿瘤背景的信号的缺乏的变化释放了EphA 2的致癌作用及其促进对放疗、化疗和靶向剂（包括表皮生长因子受体（EGFR）的抑制剂）的抗性的广泛能力。即使在RAS wt CRC患者中，高水平的EphA 2也可能降低对西妥昔单抗的应答。在这项工作中，我们的目标是审查目前的知识EphA 2功能，这是至关重要的实现一个更有效的治疗管理肿瘤耐EGFR抑制剂和许多其他药物。Eph受体代表受体酪氨酸激酶（RTK）家族中最大的一组。Eph/ephrin信号轴在发育过程中发挥着中心作用，癌症中其调节异常引起的信号传导的深度扰动揭示了其功能的多样性和复杂性。在过去的几十年中，它们已经成为实体瘤的关键参与者，包括结直肠癌（CRC）;然而，导致EphA 2在肿瘤抑制和肿瘤促进功能之间切换的原因仍然是一个活跃的研究领域。本文综述了EphA 2在癌症中的功能，详细介绍了EphA 2的癌基因-肿瘤抑制开关功能的分子决定因素的最新进展。我们描述了EphA 2信号传导的肿瘤背景特异性实例，以及EphA 2在支持癌症干细胞样群体和克服治疗诱导的应激中所起的新兴作用。在这样一个框架中，我们详细介绍了EphA 2和EGFR通路在实体瘤（包括结直肠癌）中的相互作用。我们讨论了EphA 2致癌信号对EGFR阻断剂（包括西妥昔单抗和TKI）耐药性的贡献。
The Ephrin receptors and their ligands play important roles in organ formation and tissue repair, by orchestrating complex programs of cell adhesion and repulsion, however, this same system plays a role in cancer development In fact, EphA2 levels are higher in tumors vs normal tissue and further increased upon treatment, in vivo and in vitro. Changes in the molecular status of EphA2, of its subcellular localization, the absence of ligand and signals derived from the tumor context unleash the oncogenic role of EphA2 and its broad ability to promote resistance to radiotherapy, chemotherapy and targeted agents, including inhibitors of Epidermal-Growth-Factor-Receptor (EGFR). High levels of EphA2 may reduce response to cetuximab even in RAS wt CRC patients. In this work, we aim to review the current knowledge of the EphA2 function which is crucial for achieving a more effective therapeutic management of tumors resistant to EGFR inhibitors and to many other agents. The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC); however, what causes EphA2 to switch between tumor-suppressive and tumor-promoting function is still an active theater of investigation. This review summarizes the recent advances in understanding EphA2 function in cancer, with detail on the molecular determinants of the oncogene-tumor suppressor switch function of EphA2. We describe tumor context-specific examples of EphA2 signaling and the emerging role EphA2 plays in supporting cancer—stem—cell-like populations and overcoming therapy-induced stress. In such a frame, we detail the interaction of the EphA2 and EGFR pathway in solid tumors, including colorectal cancer. We discuss the contribution of the EphA2 oncogenic signaling to the resistance to EGFR blocking agents, including cetuximab and TKIs.
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DOI：
10.1016/j.str.2018.05.003
发表时间：
2018-07-03
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Chavent M;Karia D;Kalli AC;Domański J;Duncan AL;Hedger G;Stansfeld PJ;Seiradake E;Jones EY;Sansom MSP
通讯作者：
Sansom MSP
影响因子：
50.3
作者：
Binda E;Visioli A;Giani F;Lamorte G;Copetti M;Pitter KL;Huse JT;Cajola L;Zanetti N;DiMeco F;De Filippis L;Mangiola A;Maira G;Anile C;De Bonis P;Reynolds BA;Pasquale EB;Vescovi AL
通讯作者：
Vescovi AL
生长因子介导的 Eph 受体 2 (EphA2) 激活哺乳动物雷帕霉素复合物靶标 1 (mTORC1) 和 Raf/Pyk2，是胆管癌生长和转移所必需的
影响因子：
13.5
作者：
Cui, Xiang-Dan;Lee, Mi-Jin;Kim, Dae-Ghon
通讯作者：
Kim, Dae-Ghon
影响因子：
11.5
作者：
Brannan, Jennifer M.;Dong, Wenli;Johnson, Faye M.
通讯作者：
Johnson, Faye M.
影响因子：
6.6
作者：
Allocca, Chiara;Cirafici, Anna Maria;Castellone, Maria Domenica
通讯作者：
Castellone, Maria Domenica