Hedgehog 信号通路与皮肤癌。
Hedgehog signaling in skin cancers.
机构信息
Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an 710032, China.
出版信息
Cell Signal. 2011 Aug;23(8):1235-43. doi: 10.1016/j.cellsig.2011.03.002. Epub 2011 Mar 17.
Abstract
An increasing progress on the role of Hedgehog (Hh) signaling for carcinogenesis has been achieved since the link of Hh pathway to human cancer was firstly established. In particular, the critical role of Hh signaling in the development of Basal cell carcinoma (BCC) has been convincingly demonstrated by genetic mutation analyses, mouse models of BCCs, and successful clinical trials of BCCs using Hh signaling inhibitors. In addition, the Hh pathway activity is also reported to be involved in the pathogenesis of Squamous Cell Carcinoma (SCC), melanoma and Merkel Cell Carcinoma. These findings have significant new paradigm on Hh signaling transduction, its mechanisms in skin cancer and even therapeutic approaches for BCC. In this review, we will summarize the major advances in the understanding of Hh signaling transduction, the roles of Hh signaling in skin cancer development, and the current implications of "mechanism-based" therapeutic strategies.
摘要
自首次确定 Hedgehog（Hh）信号通路与人类癌症之间的联系以来，人们在 Hedgehog（Hh）信号在致癌作用方面的研究取得了不断的进展。特别是，通过遗传突变分析、基底细胞癌（BCC）的小鼠模型以及使用 Hedgehog（Hh）信号抑制剂治疗 BCC 的成功临床试验，充分证明了 Hh 信号在 BCC 发生发展中的关键作用。此外，Hh 信号通路的活性也被报道与鳞状细胞癌（SCC）、黑色素瘤和 Merkel 细胞癌的发病机制有关。这些发现为 Hedgehog（Hh）信号转导、其在皮肤癌中的机制甚至 BCC 的治疗方法提供了新的重要范例。在这篇综述中，我们将总结对 Hedgehog（Hh）信号转导的理解、Hh 信号在皮肤癌发生发展中的作用以及“基于机制”治疗策略的当前意义方面的主要进展。
相似文献
1
Hedgehog signaling in skin cancers. Hedgehog 信号通路与皮肤癌。
Cell Signal. 2011 Aug;23(8):1235-43. doi: 10.1016/j.cellsig.2011.03.002. Epub 2011 Mar 17.
2
Advances in the treatment of Basal cell carcinoma: Hedgehog inhibitors.基底细胞癌治疗的新进展： Hedgehog 抑制剂。
Semin Oncol. 2012 Apr;39(2):139-44. doi: 10.1053/j.seminoncol.2012.01.011.
3
Loss of Primary Cilia Drives Switching from Hedgehog to Ras/MAPK Pathway in Resistant Basal Cell Carcinoma.原发性纤毛丧失驱动基底细胞癌耐药中 Hedgehog 通路向 Ras/MAPK 通路的转变。
J Invest Dermatol. 2019 Jul;139(7):1439-1448. doi: 10.1016/j.jid.2018.11.035. Epub 2019 Jan 29.
4
Synergistic cross-talk of hedgehog and interleukin-6 signaling drives growth of basal cell carcinoma. hedgehog 和白细胞介素-6 信号的协同串扰驱动基底细胞癌的生长。
Int J Cancer. 2018 Dec 1;143(11):2943-2954. doi: 10.1002/ijc.31724. Epub 2018 Oct 1.
5
Clinical implications of hedgehog signaling pathway inhibitors.刺猬信号通路抑制剂的临床意义
Chin J Cancer. 2011 Jan;30(1):13-26. doi: 10.5732/cjc.010.10540.
6
Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer.协同的刺猬因子/GLI和JAK/STAT信号通过协同诱导皮肤癌中吲哚胺2,3-双加氧酶1（IDO1）驱动免疫抑制性色氨酸/犬尿氨酸代谢。
Cell Commun Signal. 2025 Feb 17;23(1):91. doi: 10.1186/s12964-025-02101-6.
7
The role of the hedgehog signaling pathway in the development of basal cell carcinoma and opportunities for treatment. hedgehog 信号通路在基底细胞癌发生发展中的作用及治疗机会。
Clin Cancer Res. 2010 Jul 1;16(13):3335-9. doi: 10.1158/1078-0432.CCR-09-2570. Epub 2010 May 3.
8
Interaction of hedgehog and vitamin D signaling pathways in basal cell carcinomas.Hedgehog 和维生素 D 信号通路在基底细胞癌中的相互作用。
Adv Exp Med Biol. 2014;810:329-41. doi: 10.1007/978-1-4939-0437-2_18.
9
Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib.维莫德吉抑制 Hedgehog 通路对基底细胞癌和头颈部鳞状细胞癌的放射增敏作用。
Int J Mol Sci. 2018 Aug 23;19(9):2485. doi: 10.3390/ijms19092485.
10
Cross-Talk between Wnt and Hh Signaling Pathways in the Pathology of Basal Cell Carcinoma.Wnt 和 Hh 信号通路在基底细胞癌发病机制中的相互作用。
Int J Environ Res Public Health. 2018 Jul 9;15(7):1442. doi: 10.3390/ijerph15071442.
引用本文的文献
1
Drug Repurposing and Nanotechnology for Topical Skin Cancer Treatment: Redirecting toward Targeted and Synergistic Antitumor Effects.用于局部皮肤癌治疗的药物再利用与纳米技术：转向靶向和协同抗肿瘤效应
ACS Pharmacol Transl Sci. 2025 Jan 23;8(2):308-338. doi: 10.1021/acsptsci.4c00679. eCollection 2025 Feb 14.
2
Itraconazole promotes melanoma cells apoptosis via inhibiting hedgehog signaling pathway-mediated autophagy.伊曲康唑通过抑制刺猬信号通路介导的自噬促进黑色素瘤细胞凋亡。
Front Pharmacol. 2025 Jan 23;16:1545243. doi: 10.3389/fphar.2025.1545243. eCollection 2025.
3
Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients.墨西哥皮肤鳞状细胞癌患者的基因变异、mRNA表达及生物信息学见解
Biology (Basel). 2024 Mar 16;13(3):191. doi: 10.3390/biology13030191.
4
A Yeast Cell Wall Derived Hybrid Hydrogel with Photothermal and Immune Combined Modality Therapy for Enhanced Anti-Melanoma Efficacy.酵母细胞壁衍生的杂化水凝胶用于光热和免疫联合治疗以增强抗黑色素瘤疗效。
Int J Nanomedicine. 2023 Sep 21;18:5423-5440. doi: 10.2147/IJN.S409674. eCollection 2023.
5
The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.ULK3 激酶是角质形成细胞自我更新和肿瘤发生的决定因素，靶向精氨酸甲基组。
Nat Commun. 2023 Feb 16;14(1):887. doi: 10.1038/s41467-023-36410-6.
6
Advancements in nanoparticle-based treatment approaches for skin cancer therapy.基于纳米粒子的皮肤癌治疗方法的进展。
Mol Cancer. 2023 Jan 12;22(1):10. doi: 10.1186/s12943-022-01708-4.
7
Associations of keratinocyte cancers with snp variants in the sonic hedgehog pathway.角质形成细胞癌与 sonic hedgehog 通路中 snp 变异的关联。
BMC Cancer. 2022 May 3;22(1):490. doi: 10.1186/s12885-022-09565-6.
8
Skin cancer biology and barriers to treatment: Recent applications of polymeric micro/nanostructures.皮肤癌生物学与治疗障碍：高分子微/纳米结构的最新应用。
J Adv Res. 2021 Jun 16;36:223-247. doi: 10.1016/j.jare.2021.06.014. eCollection 2022 Feb.
9
Elucidating molecular mechanisms of acquired resistance to BRAF inhibitors in melanoma using a microfluidic device and deep sequencing.使用微流控装置和深度测序阐明黑色素瘤中对BRAF抑制剂获得性耐药的分子机制。
Genomics Inform. 2021 Mar;19(1):e2. doi: 10.5808/gi.20074. Epub 2021 Mar 15.
10
Recent Advances in Signaling Pathways Comprehension as Carcinogenesis Triggers in Basal Cell Carcinoma.作为基底细胞癌致癌触发因素的信号通路理解方面的最新进展
J Clin Med. 2020 Sep 18;9(9):3010. doi: 10.3390/jcm9093010.
本文引用的文献
1
Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/-) mice.基底细胞癌起源于 Ptch1(+/-) 小鼠的毛囊干细胞。
Cancer Cell. 2011 Jan 18;19(1):114-24. doi: 10.1016/j.ccr.2010.11.007. Epub 2011 Jan 6.
2
Clinical implications of hedgehog signaling pathway inhibitors.刺猬信号通路抑制剂的临床意义
Chin J Cancer. 2011 Jan;30(1):13-26. doi: 10.5732/cjc.010.10540.
3
TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling.TGF-β促进Gli2 诱导的甲状旁腺激素相关蛋白表达，该蛋白是骨转移中重要的溶骨性因子，其作用独立于经典的 Hedgehog 信号通路。
Cancer Res. 2011 Feb 1;71(3):822-31. doi: 10.1158/0008-5472.CAN-10-2993. Epub 2010 Dec 28.
4
Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas. hedgehog 信号激活与食管鳞癌放化疗敏感性及生存的相关性。
Jpn J Clin Oncol. 2011 Mar;41(3):386-93. doi: 10.1093/jjco/hyq217. Epub 2010 Dec 1.
5
Expression of the Sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck.Sonic hedgehog 通路在皮肤鳞状细胞癌和头颈部黏膜中的表达。
Head Neck. 2011 Feb;33(2):244-50. doi: 10.1002/hed.21437.
6
The molecular genetics underlying basal cell carcinoma pathogenesis and links to targeted therapeutics.基底细胞癌发病机制的分子遗传学及其与靶向治疗的关联。
J Am Acad Dermatol. 2012 May;66(5):e167-78. doi: 10.1016/j.jaad.2010.06.054. Epub 2010 Aug 30.
7
Modulators of the hedgehog signaling pathway. hedgehog 信号通路调节剂。
Bioorg Med Chem. 2010 Sep 15;18(18):6613-24. doi: 10.1016/j.bmc.2010.07.038. Epub 2010 Jul 23.
8
Novel investigational drugs for basal cell carcinoma.用于基底细胞癌的新型研究性药物。
Expert Opin Investig Drugs. 2010 Sep;19(9):1099-112. doi: 10.1517/13543784.2010.504714.
9
GLI2-mediated melanoma invasion and metastasis.GLI2 介导的黑色素瘤侵袭和转移。
J Natl Cancer Inst. 2010 Aug 4;102(15):1148-59. doi: 10.1093/jnci/djq257. Epub 2010 Jul 21.
10
Expression of hedgehog signaling molecules in lung cancer. hedgehog 信号分子在肺癌中的表达。
Acta Histochem. 2011 Sep;113(5):564-9. doi: 10.1016/j.acthis.2010.06.003. Epub 2010 Jul 24.
Zotero 插件