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Sonic Hedgehog 信号通路在妇科和泌尿生殖系统癌症中的作用(综述)。

Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review).

机构信息

Department of Histology, Faculty of Medicine, Medical University of Gdansk, 80211 Gdansk, Poland.

出版信息

Int J Mol Med. 2021 Jun;47(6). doi: 10.3892/ijmm.2021.4939. Epub 2021 Apr 28.

Abstract

Cancers of the urinary tract, as well as those of the female and male reproductive systems, account for a large percentage of malignancies worldwide. Mortality is frequently affected by late diagnosis or therapeutic difficulties. The Sonic Hedgehog (SHH) pathway is an evolutionary conserved molecular cascade, which is mainly associated with the development of the central nervous system in fetal life. The present review aimed to provide an in‑depth summary of the SHH signaling pathway, including the characterization of its major components, the mechanism of its upstream regulation and non‑canonical activation, as well as its interactions with other cellular pathways. In addition, the three possible mechanisms of the cellular SHH cascade in cancer tissue are discussed. The aim of the present review was to summarize significant findings with regards to the expression of the SHH pathway components in kidney, bladder, ovarian, cervical and prostate cancer. Reports associated with common deficits and de‑regulations of the SHH pathway were summarized, despite the differences in molecular and histological patterns among these malignancies. However, currently, neither are SHH pathway elements included in panels of prognostic/therapeutic molecular patterns in any of the discussed cancers, nor have the drugs targeting SMO or GLIs been approved for therapy. The findings of the present review may support future studies on the treatment of and/or molecular targets for gynecological and genitourinary cancers.

摘要

泌尿系统癌症以及女性和男性生殖系统癌症在全球恶性肿瘤中占很大比例。死亡率通常受到诊断较晚或治疗困难的影响。Sonic Hedgehog(SHH)信号通路是一种进化上保守的分子级联反应,主要与胎儿生命中枢神经系统的发育有关。本综述旨在深入总结 SHH 信号通路,包括其主要成分的特征、上游调控和非经典激活的机制,以及与其他细胞通路的相互作用。此外,还讨论了癌症组织中细胞 SHH 级联的三种可能机制。本综述的目的是总结 SHH 通路成分在肾、膀胱、卵巢、宫颈和前列腺癌中的表达的重要发现。总结了与 SHH 通路常见缺陷和去调控相关的报告,尽管这些恶性肿瘤在分子和组织学模式上存在差异。然而,目前,在讨论的任何一种癌症中,SHH 通路的元素都没有被纳入预后/治疗性分子模式的面板中,也没有针对 SMO 或 GLIs 的药物被批准用于治疗。本综述的结果可能为妇科和泌尿生殖系统癌症的治疗和/或分子靶点的未来研究提供支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4c/8057295/e33bc9f80626/IJMM-47-06-04939-g00.jpg

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