YAP1在肺恶性肿瘤治疗耐药性中的作用

李 玉苗1, 杨 阳1, 焦 婷1, 田 瑞2
1、河北大学附属医院
2、中国人民解放军陆军第八十二集团军医院

摘要


肺癌是全球发病率和死亡率最高的恶性肿瘤之一，早期缺乏特异性症状，确诊时多已处于中晚期。化疗仍是其主要治疗手段之一，但尽管化疗、放疗及分子靶向治疗不断进展，初始敏感患者最终仍普遍发生获得性耐药。研究表明，耐药的发生与多种耐药相关基因异常表达密切相关。Yes相关蛋白1（Yes-associated protein 1, YAP1）作为关键转录共激活因子，可通过与多种转录因子结合调控基因转录，重塑细胞生物学行为。YAP1与TEAD转录因子结合并发生核转位，驱动下游基因表达，诱导上皮间质转化，增强肿瘤细胞的增殖、迁移与侵袭能力。近年来研究进一步证实，YAP1在化疗、放疗及免疫治疗耐受中均发挥重要作用。抑制YAP1的表达或活性可显著抑制肿瘤进展并提高治疗敏感性。因此，YAP1有望成为肺癌治疗的重要干预靶点。本文系统综述了YAP1在肺癌治疗耐药中的分子机制，并探讨其作为新型治疗靶点的应用潜力。

关键词


肺癌；YAP1；耐药性；放化疗；靶点

全文:

PDF


参考


[1]de Nijs K,de Koning HJ,van der Aalst C,Ten Haaf K:Medical costs of lung cancer by stage, histology and first-line treatment modality in the Netherlands (2012-2021).European journal of cancer(Oxford,England:1990)2024,208:114231.

[2]Hou J,Li H,Ma S,He Z,Yang S,Hao L,Zhou H,Zhang Z,Han J,Wang L et al:EGFR exon 20 insertion mutations in advanced non-small-cell lung cancer:current status and perspectives. Biomarker research 2022,10(1):21.

[3]Torres GF,Bonilla CE,Buitrago G,Arrieta O,Malapelle U,Rolfo C,Cardona AF:How clinically useful is comprehensive genomic profiling for patients with non-small cell lung cancer?A systematic review.Critical reviews in oncology/hematology 2021,166:103459.

[4]Del Re M,Crucitta S,Gianfilippo G, Passaro A,Petrini I,Restante G,Michelucci A,Fogli S,de Marinis F,Porta C et al:Understanding the Mechanisms of Resistance in EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide Treatment Strategy.Int J Mol Sci 2019,20(16).

[5]Sudol M:Yes-associated protein(YAP65)is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 1994,9(8):2145-2152.

[6]Song S, Honjo S,Jin J,Chang SS,Scott AW,Chen Q, Kalhor N,Correa AM,Hofstetter WL, Albarracin CT et al:The Hippo Coactivator YAP1 Mediates EGFR Overexpression and Confers Chemoresistance in Esophageal Cancer.Clin Cancer Res 2015,21(11):2580-2590.

[7]Yoshikawa K,Noguchi K,Nakano Y,Yamamura M, Takaoka K,Hashimoto-Tamaoki T,Kishimoto H: The Hippo pathway transcriptional co-activator, YAP,confers resistance to cisplatin in human oral squamous cell carcinoma.Int J Oncol 2015, 46(6):2364-2370.

[8]Yuan Y, Li D,Li H, Wang L,Tian G,Dong Y:YAP overexpression promotes the epithelial-mesenchymal transition and chemoresistance in pancreatic cancer cells.Molecular medicine reports 2016,13(1):237-242.

[9]Hsu YL,Hung JY,Chou SH,Huang MS,Tsai MJ, Lin YS,Chiang SY, Ho YW, Wu CY,Kuo PL: Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression.Oncogene 2015,34(31):4056-4068.


Refbacks

  • 当前没有refback。