https://doi.org/10.4081/ejh.2024.4048
Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma
Submitted: 16 April 2024
Accepted: 3 July 2024
Published: 22 July 2024
Accepted: 3 July 2024
Abstract Views: 412
PDF: 166
HTML: 10
HTML: 10
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.
Kitahara CM, Schneider AB. Epidemiology of thyroid cancer. Cancer Epidemiol Biomarkers Prev 2022;31:1284-97.
DOI: https://doi.org/10.1158/1055-9965.EPI-21-1440
Wang J, Yu F, Shang Y, Ping Z, Liu L. Thyroid cancer: incidence and mortality trends in China, 2005-2015. Endocrine 2020;68:163-73.
DOI: https://doi.org/10.1007/s12020-020-02207-6
Yuan X, Li Z, Kong Y, Zhong Y, He Y, Zhang A, et al. P65 Targets FGFR1 to regulate the survival of ovarian granulosa cells. Cells 2019;8:1334.
DOI: https://doi.org/10.3390/cells8111334
Li D, Xia L, Huang P, Wang Z, Guo Q, Huang C, et al. Cancer-associated fibroblast-secreted IGFBP7 promotes gastric cancer by enhancing tumor associated macrophage infiltration via FGF2/FGFR1/PI3K/AKT axis. Cell Death Discov 2023;9:17.
DOI: https://doi.org/10.1038/s41420-023-01336-x
Hu Y, Lu Y, Xing F, Hsu W. FGFR1/MAPK-directed brachyury activation drives PD-L1-mediated immune evasion to promote lung cancer progression. Cancer Lett 2022;547:215867.
DOI: https://doi.org/10.1016/j.canlet.2022.215867
Servetto A, Kollipara R, Formisano L, Lin CC, Lee KM, Sudhan DR, et al. Nuclear FGFR1 regulates gene transcription and promotes antiestrogen resistance in ER(+) breast cancer. Clin Cancer Res 2021;27:4379-96.
DOI: https://doi.org/10.1158/1078-0432.CCR-20-3905
Yuan G, Flores NM, Hausmann S, Lofgren SM, Kharchenko V, Angulo-Ibanez M, et al. Elevated NSD3 histone methylation activity drives squamous cell lung cancer. Nature 2021;590:504-8.
DOI: https://doi.org/10.1038/s41586-020-03170-y
Murugesan K, Necchi A, Burn TC, Gjoerup O, Greenstein R, Krook M, et al. Pan-tumor landscape of fibroblast growth factor receptor 1-4 genomic alterations. ESMO Open 2022;7:100641.
DOI: https://doi.org/10.1016/j.esmoop.2022.100641
Yu T, Yang Y, Liu Y, Zhang Y, Xu H, Li M, et al. A FGFR1 inhibitor patent review: progress since 2010. Expert Opin Ther Pat 2017;27:439-54.
DOI: https://doi.org/10.1080/13543776.2017.1272574
Pfeifer A, Rusinek D, Żebracka-Gala J, Czarniecka A, Chmielik E, Zembala-Nożyńska E, et al. Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma. Genes Chromosomes Cancer 2019;58:558-66.
DOI: https://doi.org/10.1002/gcc.22737
Liu W, Zhao J, Jin M, Zhou M. circRAPGEF5 contributes to papillary thyroid proliferation and metastatis by regulation miR-198/FGFR1. Mol Ther Nucleic Acids 2019;14:609-16.
DOI: https://doi.org/10.1016/j.omtn.2019.01.003
Han S, Wang R, Zhang Y, Li X, Gan Y, Gao F, et al. The role of ubiquitination and deubiquitination in tumor invasion and metastasis. Int J Biol Sci 2022;18:2292-303.
DOI: https://doi.org/10.7150/ijbs.69411
Zheng L, Tang T, Wang Z, Sun C, Chen X, Li W, et al. FUS-mediated CircFGFR1 accelerates the development of papillary thyroid carcinoma by stabilizing FGFR1 protein. Biochem Genet 2024. Online Ahead of Print.
DOI: https://doi.org/10.1007/s10528-023-10630-3
Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, et al. The human transcription factors. Cell 2018;172:650-65.
DOI: https://doi.org/10.1016/j.cell.2018.01.029
Qin X, Jiang Q, Komori H, Sakane C, Fukuyama R, Matsuo Y, et al. Runt-related transcription factor-2 (Runx2) is required for bone matrix protein gene expression in committed osteoblasts in mice. J Bone Miner Res 2021;36:2081-95.
DOI: https://doi.org/10.1002/jbmr.4386
Henning NJ, Boike L, Spradlin JN, Ward CC, Liu G, Zhang E, et al. Deubiquitinase-targeting chimeras for targeted protein stabilization. Nat Chem Biol 2022;18:412-21.
DOI: https://doi.org/10.1038/s41589-022-00971-2
Xie P, Wang H, Xie J, Huang Z, Chen S, Cheng X, et al. USP7 promotes proliferation of papillary thyroid carcinoma cells through TBX3-mediated p57(KIP2) repression. Mol Cell Endocrinol 2020;518:111037.
DOI: https://doi.org/10.1016/j.mce.2020.111037
Li S, Zhang Z, Peng H, Xiao X. YY1-induced up-regulation of FOXE1 is negatively regulated by miR-129-5p and contributes to the progression of papillary thyroid microcarcinoma. Pathol Res Pract 2021;221:153337.
DOI: https://doi.org/10.1016/j.prp.2020.153337
Sulkshane P, Duek I, Ram J, Thakur A, Reis N, Ziv T, et al. Inhibition of proteasome reveals basal mitochondrial ubiquitination. J Proteomics 2020;229:103949.
DOI: https://doi.org/10.1016/j.jprot.2020.103949
Hu Z, Chen G, Zhao Y, Gao H, Li L, Yin Y, et al. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Mol Cancer 2023;22:55.
DOI: https://doi.org/10.1186/s12943-023-01759-1
Yao B, Zhang Q, Yang Z, An F, Nie H, Wang H, et al. CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m(6)A-modified CREB1 mRNA. Mol Cancer 2022;21:140.
DOI: https://doi.org/10.1186/s12943-022-01608-7
Wang X, Li Y, He M, Kong X, Jiang P, Liu X, et al. UbiBrowser 2.0: a comprehensive resource for proteome-wide known and predicted ubiquitin ligase/deubiquitinase-substrate interactions in eukaryotic species. Nucleic Acids Res 2022;50:D719-28.
DOI: https://doi.org/10.1093/nar/gkab962
Saha G, Roy S, Basu M, Ghosh MK. USP7 - a crucial regulator of cancer hallmarks. Biochim Biophys Acta Rev Cancer 2023;1878:188903.
DOI: https://doi.org/10.1016/j.bbcan.2023.188903
Korenev G, Yakukhnov S, Druk A, Golovina A, Chasov V, Mirgayazova R, et al. USP7 inhibitors in cancer immunotherapy: current status and perspective. Cancers (Basel) 2022;14:5539.
DOI: https://doi.org/10.3390/cancers14225539
Yang F, Zhang Y, Ressler SJ, Ittmann MM, Ayala GE, Dang TD, et al. FGFR1 is essential for prostate cancer progression and metastasis. Cancer Res 2013;73:3716-24.
DOI: https://doi.org/10.1158/0008-5472.CAN-12-3274
Shi Y, Ma Z, Cheng Q, Wu Y, Parris AB, Kong L, et al. FGFR1 overexpression renders breast cancer cells resistant to metformin through activation of IRS1/ERK signaling. Biochim Biophys Acta Mol Cell Res 2021;1868:118877.
DOI: https://doi.org/10.1016/j.bbamcr.2020.118877
Han ZJ, Feng YH, Gu BH, Li YM, Chen H. The post-translational modification, SUMOylation, and cancer (Review). Int J Oncol 2018;52:1081-94.
DOI: https://doi.org/10.3892/ijo.2018.4280
Saha G, Sarkar S, Mohanta PS, Kumar K, Chakrabarti S, Basu M, et al. USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma. Oncogene 2022;41:5061-75.
DOI: https://doi.org/10.1038/s41388-022-02486-5
Zheng N, Chu M, Lin M, He Y, Wang Z. USP7 stabilizes EZH2 and enhances cancer malignant progression. Am J Cancer Res 2020;10:299-313.
Carreira LD, Oliveira RI, Moreira VM, Salvador JAR. Ubiquitin-specific protease 7 (USP7): an emerging drug target for cancer treatment. Expert Opin Ther Targets 2023;27:1043-58.
DOI: https://doi.org/10.1080/14728222.2023.2266571
Li B, Wang J, Liao J, Wu M, Yuan X, Fang H, et al. YY1 promotes pancreatic cancer cell proliferation by enhancing mitochondrial respiration. Cancer Cell Int 2022;22:287.
DOI: https://doi.org/10.1186/s12935-022-02712-w
Tseng HY, Chen YA, Jen J, Shen PC, Chen LM, Lin TD, et al. Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression. Oncogenesis 2017;6:e313.
DOI: https://doi.org/10.1038/oncsis.2017.13
Ethics Approval
Xianning Central Hospital Institutional Ethics Committee approved the use of the human specimens (No. TDLL202209-06), This study was approved by the Xianning Central Hospital Animal Care and Use Committee (IACUC, No. ANHB202303-08)How to Cite
Li, X. B., Li, J. L., Wang, C., Zhang, Y., & Li, J. (2024). Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4048
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Zhiyang Wang, Jing Li, Ziwei Liu, Ling Yue, Nrf2 as a novel diagnostic biomarker for papillary thyroid carcinoma , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- S.A. Ferreira, J.L.A. Vasconcelos, R.C.W.C. Silva, C.L.B. Cavalcanti, C.L. Bezerra, M.J.B.M. Rêgo, E.I.C. Beltrão, Expression patterns of α2,3-Sialyltransferase I and α2,6-Sialyltransferase I in human cutaneous epithelial lesions , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- R. M. Ruggeri, E. Vitarelli, G. Barresi, F. Trimarchi, S. Benvenga, M. Trovato, The tyrosine kinase receptor c-met, its cognate ligand HGF and the tyrosine kinase receptor trasducers STAT3, PI3K and RHO in thyroid nodules associated with Hashimoto's thyroiditis: an immunohistochemical characterization , European Journal of Histochemistry: Vol. 54 No. 2 (2010)
- M. Artico, E. Bronzetti, V. Alicino, B. Ionta, S. Bosco, C. Grande, M. Bruno, F. M. Tranquilli Leali, G. Ionta, L. Fumagalli, Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3 , European Journal of Histochemistry: Vol. 54 No. 1 (2010)
- C. Cui, P. Lal, S. Master, Y. Ma, T. Baradet, Z. Bing, Expression of parafibromin in major renal cell tumors , European Journal of Histochemistry: Vol. 56 No. 4 (2012)
- Yan Wang, Jie Sun, Ninghua Yao, Correlation of the AKT/mTOR signaling pathway with the clinicopathological features and prognosis of nasopharyngeal carcinoma , European Journal of Histochemistry: Vol. 65 No. 4 (2021)
- S. Soddu, E. Di Felice, S. Cabras, M.E. Castellanos, L. Atzori, G. Faa, L. Pilloni, IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- Z. Protrka, S. Arsenijevic, A. Dimitrijevic, S. Mitrovic, V. Stankovic, M. Milosavljevic, T. Kastratovic, J. Djuric, Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions , European Journal of Histochemistry: Vol. 55 No. 1 (2011)
- Ying Wang, Shifa Yuan, Jing Ma, Hong Liu, Lizhen Huang, Fengzhen Zhang, Substance P is overexpressed in cervical squamous cell carcinoma and promoted proliferation and invasion of cervical cancer cells in vitro , European Journal of Histochemistry: Vol. 67 No. 3 (2023)
- Z. Shen, Y. Ren, D. Ye, J. Guo, C. Kang, H. Ding, Significance and relationship between DJ-1 gene and survivin gene expression in laryngeal carcinoma , European Journal of Histochemistry: Vol. 55 No. 1 (2011)
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
1
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
96
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
