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刺猬索尼基因-胶质瘤相关癌基因同源物1信号通路在侵袭性和转移性乳腺癌中的预后作用

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers.

作者信息

Rokkam Prasuja, Gugalavath Shailender, Gift Kumar Deepak Kakara, Vempati Rahul Kumar, Malla Rama Rao

机构信息

Cancer Biology Lab, Department of Biochemistry & Bioinformatics, GIS, GITAM Institute of Science, Visakhapatnam, Andhra Pradesh 530045, India.

出版信息

Curr Drug Metab. 2020;21(1):33-43. doi: 10.2174/1389200221666200122120625.

Abstract

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5' and 3'- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

摘要

胶质瘤相关癌基因同源物1(GLI1)被报道为人类胶质母细胞瘤细胞中的一个扩增基因。它是一种类克鲁ppel转录因子,属于锌指家族。GLI1的基本功能是人类不同阶段的正常神经发育。GLI1基因最初定位于染色体亚带12q13.3 - 14.1。此外,除了两个转录后剪接变体GLIΔN和tGLI外,在GLI1基因5'和3'-UTR的翻译区域大多观察到单核苷酸多态性。此外,它还调节大量基因,这些基因介导增殖、分化、肿瘤发生、上皮-间质转化和转移等关键细胞过程。它还调节肿瘤耐受性、化疗耐药性和放疗耐药性。GLI1的异常表达预示着乳腺癌患者的不良生存。GLI1是SHH信号通路的重要介质,调节干细胞的自我更新、血管生成以及FOXS1、CYR61的表达。GLI1介导的HH通路可诱导凋亡。因此,GLI1可能成为未来乳腺癌诊断、预后的标志物以及有效的治疗靶点。

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