Significance of talin in cancer progression and metastasis.
Significance of talin in cancer progression and metastasis.
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DOI：
10.1016/b978-0-12-386039-2.00004-3
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发表时间：
2011
影响因子：
--
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Desiniotis A;Kyprianou N
在从细胞外基质脱离后，肿瘤上皮细胞和肿瘤相关内皮细胞能够克服失巢凋亡，获得存活益处，并因此有助于转移过程。粘着斑复合物的形成募集关键衔接蛋白如FAK（粘着斑激酶）的缔合。波形蛋白、桩蛋白和talin负责介导肌动蛋白细胞骨架和整合素之间的相互作用。Talin是一种早期募集的局灶性粘附参与者，其在介导与整联蛋白胞质尾的相互作用中具有结构和功能意义，导致跨膜复合物的不稳定，并导致介导整联蛋白活化的细胞外整联蛋白隔室中的重排。Talin介导的整合素活化在整合素介导的信号传导和诱导下游存活途径中起决定性作用，导致保护免于失巢凋亡，并因此导致癌症进展至转移。我们最近报道，与良性和正常前列腺组织相比，talin在前列腺癌中的表达显著增加，并且这种过度表达与转移性疾病的进展相关，这暗示了talin在肿瘤进展期间的预后价值。在分子水平上，talin在功能上与增强的存活和增殖途径相关，并通过激活Akt存活途径赋予原发性肿瘤细胞的失巢凋亡抗性和转移性扩散。在这篇综述中，我们讨论了越来越多的证据，周围的价值塔林作为一个预后标志物的癌症进展到转移，并作为治疗目标，在晚期前列腺癌，以及目前的理解机制，调节其信号活性在癌症中。
Upon detachment from the extracellular matrix, tumor epithelial cells and tumor-associated endothelial cells are capable of overcoming anoikis, gain survival benefits, and hence contribute to the process of metastasis. The focal-adhesion complex formation recruits the association of key adaptor proteins such as FAK (focal-adhesion kinase). Vimentin, paxillin, and talin are responsible for mediating the interaction between the actin cytoskeleton and integrins. Talin is an early-recruited focal-adhesion player that is of structural and functional significance in mediating interactions with integrin cytoplasmic tails leading to destabilization of the transmembrane complex and resulting in rearrangements in the extracellular integrin compartments that mediate integrin activation. Talin-mediated integrin activation plays a definitive role in integrin-mediated signaling and induction of downstream survival pathways leading to protection from anoikis and consequently resulting in cancer progression to metastasis. We recently reported that talin expression is significantly increased in prostate cancer compared with benign and normal prostate tissue and that this overexpression correlates with progression to metastatic disease implicating a prognostic value for talin during tumor progression. At the molecular level, talin is functionally associated with enhanced survival and proliferation pathways and confers anoikis resistance and metastatic spread of primary tumor cells via activation of the Akt survival pathway. In this review, we discuss the growing evidence surrounding the value of talin as a prognostic marker of cancer progression to metastasis and as therapeutic target in advanced prostate cancer, as well as the current understanding of mechanisms regulating its signaling activity in cancer.