Academic Journal

NGF Signaling Interacts With the Hippo/YAP Pathway to Regulate Cervical Cancer Progression

التفاصيل البيبلوغرافية
العنوان: NGF Signaling Interacts With the Hippo/YAP Pathway to Regulate Cervical Cancer Progression
المؤلفون: Lijun Wang, Jing Li, Rongli Wang, He Chen, Ruiqi Wang, Wei Wang, Xinyuan Yang
المصدر: Frontiers in Oncology, Vol 11 (2021)
بيانات النشر: Frontiers Media S.A., 2021.
سنة النشر: 2021
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: cervical cancer, LATS1, NGF, progression, YAP, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Nerve growth factor (NGF) is increasingly implicated in cervical cancer progression, but its mechanism in cervical cancer is unclear. Here, studies demonstrate that NGF inhibits the Hippo signaling pathway and activates Yes-associated protein (YAP) to induce cervical cancer cell proliferation and migration. Our results suggested that stimulation of NGF promoted cell growth and migration and activated YAP in HeLa and C-33A cell lines. The expression of YAP target genes (CTGF and ANKRD1) was upregulated after NGF treatment. The NGF inhibitor Ro 08-2750 and siRNA-mediated NGF receptor gene silencing suppressed HeLa and C-33A cells proliferation and migration, activated large suppressor kinase 1 (LATS1) kinase activity, and suppressed YAP function. In addition, the expression of YAP target genes (CTGF and ANKRD1) was suppressed by Ro 08-2750 treatment in HeLa and C-33A cells. Interestingly, proliferation was significantly higher in NGF-treated cells than in control cells, and this effect was completely reversed by the YAP small molecule inhibitor-verteporfin. Furthermore, the mouse xenograft model shows that NGF regulates YAP oncogenic activity in vivo. Mechanistically, NGF stimulation inactivates LATS1 and activates YAP, and NGF inhibition was found to induce large suppressor kinase 1 (LATS1) phosphorylation. Taken together, these data provide the first direct evidence of crosstalk between the NGF signaling and Hippo cancer pathways, an interaction that affects cervical cancer progression. Our study indicates that combined targeting of the NGF signaling and the Hippo pathway represents a novel therapeutic strategy for treatment of cervical cancer.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2234-943X
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2021.688794/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2021.688794
URL الوصول: https://doaj.org/article/b808cfe7bb394ce0b5afc4506815e283
رقم الانضمام: edsdoj.b808cfe7bb394ce0b5afc4506815e283
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2021.688794