Sonic Hedgehog in cancer stem cells: a novel link with autophagy
Sonic Hedgehog in cancer stem cells: a novel link with autophagy
复制标题
DOI：
10.4067/s0716-97602012000300004
复制
发表时间：
2012-01-01
影响因子：
6.7
通讯作者：
Palma, Verónica
中科院分区：
文献类型：
--
作者：
Milla, Luis A;González-Ramírez, Claudia N;Palma, Verónica
Sonic Hegdehog/GLI（SHH/GLI）通路因其在发育和癌症生物学中的作用而被广泛研究。在早期胚胎发育过程中，SHH途径主要参与模式形成，而在后期阶段，其在干细胞和祖细胞增殖中的功能变得越来越相关。在出生后发育和成年组织中，SHH/GLI通过积极调节基因转录促进细胞稳态，重现正常组织生长期间观察到的功能。在这篇综述中，我们将简要讨论SHH/GLI在肿瘤生长和癌症演变中的根本重要性，然后我们将通过癌症干细胞中的自噬调节提供SHH在癌症中作用的可能新机制的见解。自噬是一种稳态机制，当被破坏时，可以促进和加速癌细胞和具有肿瘤发生的基质中的肿瘤进展。了解SHH信号传导的可能新靶点及其通过调节自噬对癌症的贡献可能会提供更好的策略，以便设计联合治疗并进行临床试验。
The Sonic Hegdehog/GLI (SHH/GLI) pathway has been extensively studied for its role in developmental and cancer biology. During early embryonic development the SHH pathway is involved mainly in pattern formation, while in latter stages its function in stem cell and progenitor proliferation becomes increasingly relevant. During postnatal development and in adult tissues, SHH/GLI promotes cell homeostasis by actively regulating gene transcription, recapitulating the function observed during normal tissue growth. In this review, we will briefly discuss the fundamental importance of SHH/GLI in tumor growth and cancer evolution and we will then provide insights into a possible novel mechanism of SHH action in cancer through autophagy modulation in cancer stem cells. Autophagy is a homeostatic mechanism that when disrupted can promote and accelerate tumor progression in both cancer cells and the stroma that harbors tumorigenesis. Understanding possible new targets for SHH signaling and its contribution to cancer through modulation of autophagy might provide better strategies in order to design combined treatments and perform clinical trials.