Hedgehog信號(hào)通路在肺癌中的研究進(jìn)展

付政超　呼群

【摘要】 肺癌發(fā)病率高、預(yù)后差，其發(fā)生過(guò)程涉及多個(gè)信號(hào)通路的異常改變，其中Hedgehog通路在肺癌中的作用逐漸被發(fā)現(xiàn)，Hedgehog通路最早發(fā)現(xiàn)于果蠅胚胎發(fā)育過(guò)程，近來(lái)發(fā)現(xiàn)其涉及了肺、消化等多個(gè)組織器官的發(fā)育及癌變過(guò)程，特別是肺癌中發(fā)現(xiàn)，Hedgehog通路的異常激活參與了肺癌的耐藥、增殖、轉(zhuǎn)移等過(guò)程。本文從Hedgehog信號(hào)通概述、Hedgehog在小細(xì)胞肺癌中的作用、非小細(xì)胞肺癌增殖、耐藥中的作用進(jìn)行綜述分析，旨在為Hedgehog通路在肺癌的研究提供新的思路及尋找肺癌治療的新靶點(diǎn)。

【關(guān)鍵詞】 Hedgehog信號(hào)通路; 肺癌

Advances in Hedgehog Signaling Pathway in Lung Cancer/FU Zhengchao，HU Qun.//Medical Innovation of China，2019，16（06）：-172

【Abstract】 Lung cancer has a high incidence and poor prognosis，its occurrence process involves abnormal changes of multiple signaling pathways，the role of Hedgehog signaling pathway in lung cancer has been gradually discovered.Hedgehog signaling pathway was the first found in the embryonic development of Drosophila melanogaster.Recently，it has been found that Hedgehog signaling pathway involves the development and canceration of lung，digestion and other tissues and organs，in particular.It is found that the abnormal activation of Hedgehog signaling pathway is involved in the process of drug resistance，proliferation and metastasis of lung cancer.This article reviews the role of Hedgehog signaling pathway in small cell lung cancer，proliferation and drug resistance of non-small cell lung cancer，in order to provide new ideas for the study of Hedgehog signaling pathway in lung cancer，path and search for new targets for lung cancer treatment.

【Key words】 Hedgehog signaling pathway; Lung cancer

First-authors address：Inner Mongolia Medical University，Hohhot 010110，China

doi：10.3969/j.issn.1674-4985.2019.06.045

肺癌是最常見的惡性腫瘤之一，預(yù)后差、致死率高。2018年全球肺癌新發(fā)病例210萬(wàn)人，死亡病例180萬(wàn)人，占癌癥死亡人數(shù)的近1/5（18.4%），并且在中國(guó)仍是男性腫瘤死亡的主要原因[1-2]，有數(shù)據(jù)提示57%的非小細(xì)胞肺癌患者診斷時(shí)已有遠(yuǎn)端轉(zhuǎn)移[3-5]。而肺癌的發(fā)生、轉(zhuǎn)移及耐藥等過(guò)程涉及了包括Hedgehog、Went等多個(gè)信號(hào)傳導(dǎo)調(diào)控過(guò)程，但具體調(diào)控機(jī)制尚未清晰。本文從Hedgehog信號(hào)通路的概述，小細(xì)胞肺癌中Hedgehog的作用，非小細(xì)胞肺癌增殖、耐藥中Hedgehog的作用進(jìn)行綜述分析，從而發(fā)現(xiàn)目前研究Hedgehog信號(hào)通路在肺癌中調(diào)控的新觀點(diǎn)。

1 Hedgehog信號(hào)通路概述

Hedgehog信號(hào)通路首次發(fā)現(xiàn)并證實(shí)參與了果蠅胚胎的發(fā)育過(guò)程，經(jīng)典的Hedgehog信號(hào)通路組成包括配體蛋白Indian Hedgehog（IHh）、Desert Hedgehog（DHh）和Sonic Hedgehog（SHh）;膜受體蛋白Patched（Ptch）和Smoothened（Smo）和目前發(fā)現(xiàn)的核內(nèi)轉(zhuǎn)錄因子Ci/Gli、SuFu、COX2、PKA和cAMP等。

1.1 Hedgehog配體 經(jīng)典的Hedgehog配體主要有IHh、DHh和SHh。人類SHh由位于7q36.3的SHh基因編輯，已證實(shí)參與了胚胎發(fā)育時(shí)候誘導(dǎo)如中樞神經(jīng)、肺、腸道等組織器官的發(fā)育。……