The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.
The Hedgehog-GLI pathway in embryonic development and cancer: implications for pulmonary oncology therapy.
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DOI：
10.18632/oncotarget.19527
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发表时间：
2017-09-01
期刊：
影响因子：
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通讯作者：
Ávila-Moreno F
中科院分区：
文献类型：
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作者：
Armas-López L;Zúñiga J;Arrieta O;Ávila-Moreno F
转录调控和表观遗传机制通过多种生理和病理生理过程密切控制着基因的表达。这些包括胚层的发育和出生后上皮细胞组织分化，以及参与诱导、促进和/或人类恶性肿瘤的进展。不同的研究揭示了上皮源性恶性肿瘤胚胎上皮发育阶段和去分化过程中的分子异同，其中许多研究集中在肺癌上。在肺癌中，一些转录、表观遗传和遗传畸变已被描述为部分由环境风险因素引起，但种族遗传易感性因素也可能起作用。癌症分子特征的分类对于研究和全面了解细胞信号通路之间的相互作用网络以及转录和表观遗传调控机制的功能作用至关重要。这反过来又增加了对这些分子网络如何参与胚胎层和恶性疾病发展的理解。最终，生物医学的一个主要目标是全面了解它们在肺肿瘤患者中作为诊断、预后和治疗反应指标的作用。最近，基于促进和/或调节不同癌症特征的作用，人们研究了几种显著的细胞信号通路，其中包括基因组不稳定、增殖信号加剧、复制不朽、肿瘤侵袭-转移、炎症和免疫监视逃避机制。其中，Hedgehog-GLI （Hh）细胞信号通路已被确定为上述几种功能性胚胎恶性肿瘤过程的主要分子贡献。尽管如此，对调控表观遗传和转录机制的系统研究仍未被探索，这可以确定恶性肿瘤进展和肺肿瘤治疗耐药中特定生物标志物和/或新治疗靶点之间的相互作用网络。在目前的工作中，我们旨在修订生物学、胚胎学和癌症研究中有关Hh通路的最重要的最新实验和临床发现。我们探索了与Hh-GLI细胞信号通路成员相关的转录-表观遗传编程与重编程机制的潜在控制。最后，我们对这些信息进行总结，以系统地整合Hh信号通路，以确定并提出新的复合策略或更好的肺癌肿瘤治疗方案。
Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas. In lung cancer, several transcriptional, epigenetic and genetic aberrations have been described to partly arise from environmental risk factors, but ethnic genetic predisposition factors may also play a role. The classification of the molecular hallmarks of cancer has been essential to study and achieve a comprehensive view of the interaction networks between cell signaling pathways and functional roles of the transcriptional and epigenetic regulatory mechanisms. This has in turn increased understanding on how these molecular networks are involved in embryo-layers and malignant diseases development. Ultimately, a major biomedicine goal is to achieve a thorough understanding of their roles as diagnostic, prognostic and treatment response indicators in lung oncological patients. Recently, several notable cell-signaling pathways have been studied based on their contribution to promoting and/or regulating the engagement of different cancer hallmarks, among them genome instability, exacerbated proliferative signaling, replicative immortality, tumor invasion-metastasis, inflammation, and immune-surveillance evasion mechanisms. Of these, the Hedgehog-GLI (Hh) cell-signaling pathway has been identified as a main molecular contribution into several of the abovementioned functional embryo-malignancy processes. Nonetheless, the systematic study of the regulatory epigenetic and transcriptional mechanisms has remained mostly unexplored, which could identify the interaction networks between specific biomarkers and/or new therapeutic targets in malignant tumor progression and resistance to lung oncologic therapy. In the present work, we aimed to revise the most important up-to-date experimental and clinical findings in biology, embryology and cancer research regarding the Hh pathway. We explore the potential control of the transcriptional-epigenetic programming versus reprogramming mechanisms associated with its Hh-GLI cell signaling pathway members. Last, we present a summary of this information to systematically integrate the Hh signaling pathway to identify and propose novel compound strategies or better oncological therapeutic schemes for lung cancer patients.