c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.
c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.
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DOI：
10.3389/fcell.2022.994528
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
c-Met是一种受体酪氨酸激酶，其在被其配体肝细胞生长因子激活后，介导调节细胞功能如存活、增殖和迁移的许多重要信号传导途径。它的致癌和致瘤信号机制，大大有助于癌症的发展和进展，是有据可查的。整合素是促进细胞-细胞外基质相互作用的异质性粘附受体，在生物力学敏感的细胞粘附和运动中非常重要，而且还调节多种细胞行为。在这里，我们回顾了c-Met和几种整合素，特别是β1和β4，在各种细胞模型，包括许多肿瘤细胞类型之间的合作的研究报告。从各种实验模型和结果分析，我们提出，c-Met整合素合作发生通过内向外或外信号。因此，c-Met活化触发整联蛋白活化和细胞粘附，或者整联蛋白粘附至其细胞外配体触发c-Met活化。这两种合作模式需要整合素的粘附功能，并且主要导致细胞迁移和侵袭。在第三种不太传统的合作模式中，整合素起着c-Met的信号适配器的作用，独立于其粘附特性，导致锚定独立生存。最近的研究已经揭示了内吞运输在c-Met-整联蛋白合作中的影响，包括在内膜上发生的整联蛋白的衔接子功能，触发内部信号传导，被认为促进转移细胞的存活。我们提出了在体内和人体组织中的合作的证据，并强调其治疗相关性。更好地理解调节c-Met-整联蛋白在癌症进展中的合作的机制可能导致设计针对这种合作的新疗法，提供比临床中使用的c-Met或整联蛋白抑制剂作为单一疗法更有效的治疗方法。
c-Met is a receptor tyrosine kinase which upon activation by its ligand, the hepatocyte growth factor, mediates many important signalling pathways that regulate cellular functions such as survival, proliferation, and migration. Its oncogenic and tumorigenic signalling mechanisms, greatly contributing to cancer development and progression, are well documented. Integrins, heterogeneous adhesion receptors which facilitate cell-extracellular matrix interactions, are important in biomechanically sensitive cell adhesion and motility but also modulate diverse cell behaviour. Here we review the studies which reported cooperation between c-Met and several integrins, particularly β1 and β4, in various cell models including many tumour cell types. From the various experimental models and results analysed, we propose that c-Met-integrin cooperation occurs via inside-out or outside-in signalling. Thus, either c-Met activation triggers integrin activation and cell adhesion or integrin adhesion to its extracellular ligand triggers c-Met activation. These two modes of cooperation require the adhesive function of integrins and mostly lead to cell migration and invasion. In a third, less conventional, mode of cooperation, the integrin plays the role of a signalling adaptor for c-Met, independently from its adhesive property, leading to anchorage independent survival. Recent studies have revealed the influence of endocytic trafficking in c-Met-integrin cooperation including the adaptor function of integrin occurring on endomembranes, triggering an inside-in signalling, believed to promote survival of metastatic cells. We present the evidence of the cooperation in vivo and in human tissues and highlight its therapeutic relevance. A better understanding of the mechanisms regulating c-Met-integrin cooperation in cancer progression could lead to the design of new therapies targeting this cooperation, providing more effective therapeutic approaches than c-Met or integrin inhibitors as monotherapies used in the clinic.
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影响因子：
21.3
作者：
Alanko J;Mai A;Jacquemet G;Schauer K;Kaukonen R;Saari M;Goud B;Ivaska J
通讯作者：
Ivaska J
影响因子：
4
作者：
Bridgewater, Rebecca E.;Norman, Jim C.;Caswell, Patrick T.
通讯作者：
Caswell, Patrick T.
DOI：
10.1083/jcb.142.4.1145
发表时间：
1998-08-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Trusolino L;Serini G;Cecchini G;Besati C;Ambesi-Impiombato FS;Marchisio PC;De Filippi R
通讯作者：
De Filippi R
影响因子：
4
作者：
De Franceschi N;Hamidi H;Alanko J;Sahgal P;Ivaska J
通讯作者：
Ivaska J
DOI：
10.1016/j.biocel.2014.01.009
发表时间：
2014-04-01
影响因子：
4
作者：
Barrow-McGee, Rachel;Kermorgant, Stephanie
通讯作者：
Kermorgant, Stephanie