CBX8 Promotes Epithelial-mesenchymal Transition, Migration, and Invasion of Lung Cancer through Wnt/β-catenin Signaling Pathway


如何引用文章

全文:

详细

Background:Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression.

Methods:Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ β-catenin signaling pathway were detected by western blot.

Results:Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/β-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/β-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8.

Conclusion:Collectively, these data demonstrated that CBX8 induced EMT through Wnt/β-- catenin signaling, driving migration and invasion of LC cells.

作者简介

Xiaoping Cai

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Yuankai Lv

Department of Respiratory, x affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Jiongwei Pan

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Zhuo Cao

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Junzhi Zhang

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Yuling Li

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

Email: info@benthamscience.net

Hao Zheng

Department of Respiratory, Six affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. Salem, H.S. Cancer status in the occupied palestinian territories: Types; incidence; mortality; sex, age, and geography distribution; and possible causes. J. Cancer Res. Clin. Oncol., 2022, 1-25. doi: 10.1007/s00432-022-04430-2 PMID: 36350411
  2. Nigro, O.; Tuzi, A.; Coppola, A.; Tartaro, T.; Chini, C.; Pinotti, G. Combination of radiation therapy for brain metastasis and anti-PD-1/PD-L1 treatment in non-small cell lung cancer: Two cases and review of the literature. Anticancer Drugs, 2021, 32(4), 460-464. doi: 10.1097/CAD.0000000000000996 PMID: 33587349
  3. Liu, B. Current treatment status and prospect of surgery and thermal ablation for pulmonary oligometastases in non-small cell lung cancer. Zhongguo Fei Ai Za Zhi, 2023, 26(3), 238-244. doi: 10.3779/j.issn.1009-3419.2023.106.06 PMID: 37035886
  4. Vinod, S.K.; Hau, E. Radiotherapy treatment for lung cancer: Current status and future directions. Respirology, 2020, 25(S2), 61-71. doi: 10.1111/resp.13870 PMID: 32516852
  5. Zhao, Y.; Yu, L.; Wang, L.; Wu, Y.; Chen, H.; Wang, Q.; Wu, Y. Current status of and progress in the treatment of malignant pleural effusion of lung cancer. Front. Oncol., 2023, 12, 961440. doi: 10.3389/fonc.2022.961440 PMID: 36818672
  6. Carter, B.W.; Halpenny, D.F.; Ginsberg, M.S.; Papadimitrakopoulou, V.A.; de Groot, P.M. Immunotherapy in non–small cell lung cancer treatment. J. Thorac. Imaging, 2017, 32(5), 300-312. doi: 10.1097/RTI.0000000000000291 PMID: 28786858
  7. Yan, N.; Guo, S.; Zhang, H.; Zhang, Z.; Shen, S.; Li, X. BRAF-mutated non-small cell lung cancer: Current treatment status and future perspective. Front. Oncol., 2022, 12, 863043. doi: 10.3389/fonc.2022.863043 PMID: 35433454
  8. Lechevalier, T.; Lynch, T. Adjuvant treatment of lung cancer: Current status and potential applications of new regimens. Lung Cancer, 2004, 46(Suppl. 2), S33-S39. doi: 10.1016/S0169-5002(04)80039-4 PMID: 15698530
  9. Aldawsari, H.M.; Singh, S.; Alhakamy, N.A.; Bakhaidar, R.B.; Halwani, A.A.; Sreeharsha, N.; Badr-Eldin, S.M. Adenosine conjugated docetaxel nanoparticles-proof of concept studies for non-small cell lung cancer. Pharmaceuticals, 2022, 15(5), 544. doi: 10.3390/ph15050544 PMID: 35631370
  10. Tang, B.; Tian, Y.; Liao, Y.; Li, Z.; Yu, S.; Su, H.; Zhong, F.; Yuan, G.; Wang, Y.; Yu, H.; Tomlinson, S.; Qiu, X.; He, S. CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma. Cell Death Dis., 2019, 10(2), 52. doi: 10.1038/s41419-018-1288-0 PMID: 30718464
  11. Wang, S.; Denton, K.E.; Hobbs, K.F.; Weaver, T.; McFarlane, J.M.B.; Connelly, K.E.; Gignac, M.C.; Milosevich, N.; Hof, F.; Paci, I.; Musselman, C.A.; Dykhuizen, E.C.; Krusemark, C.J. Optimization of ligands using focused DNA-encoded libraries to develop a selective, cell-permeable cbx8 chromodomain inhibitor. ACS Chem. Biol., 2020, 15(1), 112-131. doi: 10.1021/acschembio.9b00654 PMID: 31755685
  12. Chen, A.C.H.; Peng, Q.; Fong, S.W.; Lee, K.C.; Yeung, W.S.B.; Lee, Y.L. DNA damage response and cell cycle regulation in pluripotent stem cells. Genes, 2021, 12(10), 1548. doi: 10.3390/genes12101548 PMID: 34680943
  13. Zeng, F.; Luo, L.; Li, D.; Guo, J.; Guo, M. KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway. J. Transl. Med., 2021, 19(1), 112. doi: 10.1186/s12967-021-02709-5 PMID: 33731128
  14. Wu, Y.; Duan, Y.; Li, X.; Zhao, R.; Lan, B.; Zhang, X.; Wang, X.; Chen, H.; Feng, S.; Liu, Z.; Cheng, Y.; Xi, L.; Wang, Y.; Xue, F.; Xuan, C. CBX8 together with set facilitates ovarian carcinoma growth and metastasis by suppressing the transcription of SUSD2. Mol. Cancer Res., 2022, 20(11), 1611-1622. doi: 10.1158/1541-7786.MCR-22-0139 PMID: 35894945
  15. Meng, Q.; Li, L.; Wang, L. High CBX8 Expression leads to poor prognosis in laryngeal squamous cell carcinoma by inducing EMT by activating the Wnt/β-catenin signaling pathway. Front. Oncol., 2022, 12, 881262. doi: 10.3389/fonc.2022.881262 PMID: 35814427
  16. He, N.; Wang, Y.; Zhang, C.; Wang, M.; Wang, Y.; Zuo, Q.; Zhang, Y.; Li, B. Wnt signaling pathway regulates differentiation of chicken embryonic stem cells into spermatogonial stem cells via Wnt5a. J. Cell. Biochem., 2018, 119(2), 1689-1701. doi: 10.1002/jcb.26329 PMID: 28786525
  17. Kong, L.; Yu, Y.; Guan, H.; Jiang, L.; Sun, F.; Li, X.; Huang, W.; Li, B. TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β-catenin and Akt/mTOR signaling pathways. Int. J. Mol. Med., 2021, 47(5), 77. doi: 10.3892/ijmm.2021.4910 PMID: 33693954
  18. Zhao, X.; Ma, L.; Dai, L.; Zuo, D.; Li, X.; Zhu, H.; Xu, F. TNF-α promotes the malignant transformation of intestinal stem cells through the NF-κB and Wnt/β-catenin signaling pathways. Oncol. Rep., 2020, 44(2), 577-588. doi: 10.3892/or.2020.7631 PMID: 32627006
  19. Jiang, L.; Li, J.; Zhang, C.; Shang, Y.; Lin, J. YAP-mediated crosstalk between the Wnt and Hippo signaling pathways (Review). Mol. Med. Rep., 2020, 22(5), 4101-4106. doi: 10.3892/mmr.2016.5010 PMID: 33000236
  20. Robinson, K.F.; Narasipura, S.D.; Wallace, J.; Ritz, E.M.; Al-Harthi, L. β-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes. Cell Commun. Signal., 2020, 18(1), 93. doi: 10.1186/s12964-020-00565-2 PMID: 32546183
  21. Fröhlich, J.; Rose, K.; Hecht, A. Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival and propagation of multiple human colorectal cancer cell lines. Sci. Rep., 2023, 13(1), 287. doi: 10.1038/s41598-022-27261-0 PMID: 36609428
  22. Yu, F.; Yu, C.; Li, F.; Zuo, Y.; Wang, Y.; Yao, L.; Wu, C.; Wang, C.; Ye, L. Wnt/β-catenin signaling in cancers and targeted therapies. Signal Transduct. Target. Ther., 2021, 6(1), 307. doi: 10.1038/s41392-021-00701-5 PMID: 34456337
  23. Chen, Y.; Song, W. Wnt/catenin β1/microRNA 183 predicts recurrence and prognosis of patients with colorectal cancer. Oncol. Lett., 2018, 15(4), 4451-4456. doi: 10.3892/ol.2018.7886 PMID: 29541213
  24. Sun, Q.; Fu, Q.; Li, S.; Li, J.; Liu, S.; Wang, Z.; Su, Z.; Song, J.; Lu, D. Emetine exhibits anticancer activity in breast cancer cells as an antagonist of Wnt/β-catenin signaling. Oncol. Rep., 2019, 42(5), 1735-1744. doi: 10.3892/or.2019.7290 PMID: 31436297
  25. He, S.; Tang, S. WNT/β-catenin signaling in the development of liver cancers. Biomed. Pharmacother., 2020, 132, 110851. doi: 10.1016/j.biopha.2020.110851 PMID: 33080466
  26. Chen, H.; Zhao, J.; Jiang, N.; Wang, Z.; Liu, C. hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β-catenin signaling pathway. Anticancer. Agents Med. Chem., 2021, 21(18), 2592-2602. doi: 10.2174/1871520621666210201095613 PMID: 33563184
  27. Wang, H.; Zhang, P. lncRNA-CASC15 promotes osteosarcoma proliferation and metastasis by regulating epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. Oncol. Rep., 2021, 45(5), 76. doi: 10.3892/or.2021.8027 PMID: 33760218
  28. Brims, F.J.; McWilliams, A.; Harden, S.V.; O’Byrne, K. Lung cancer: Progress with prognosis and the changing state of play. Med. J. Aust., 2022, 216(7), 334-336. doi: 10.5694/mja2.51474 PMID: 35352375
  29. Cheng, N.; Liu, J.; Chen, C.; Zheng, T.; Li, C.; Huang, J. Prediction of lung cancer metastasis by gene expression. Comput. Biol. Med., 2023, 153, 106490. doi: 10.1016/j.compbiomed.2022.106490 PMID: 36638618
  30. Lin, L.; Li, M.; Lin, L.; Xu, X.; Jiang, G.; Wu, L. FPPS mediates TGF-β1-induced non-small cell lung cancer cell invasion and the EMT process via the RhoA/Rock1 pathway. Biochem. Biophys. Res. Commun., 2018, 496(2), 536-541. doi: 10.1016/j.bbrc.2018.01.066 PMID: 29337059
  31. Wang, D.; Bu, F.; Zhang, W. The role of ubiquitination in regulating embryonic stem cell maintenance and cancer development. Int. J. Mol. Sci., 2019, 20(11), 2667. doi: 10.3390/ijms20112667 PMID: 31151253
  32. Jia, Y.; Wang, Y.; Zhang, C.; Chen, M.Y. Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway. Mol. Ther. Oncolytics, 2020, 19, 188-196. doi: 10.1016/j.omto.2020.09.012 PMID: 33251331
  33. Dinicola, S.; Masiello, M.G.; Proietti, S.; Coluccia, P.; Fabrizi, G.; Catizone, A.; Ricci, G.; de Toma, G.; Bizzarri, M.; Cucina, A. Nicotine increases colon cancer cell migration and invasion through epithelial to mesenchymal transition (EMT): COX-2 involvement. J. Cell. Physiol., 2018, 233(6), 4935-4948. doi: 10.1002/jcp.26323 PMID: 29215713
  34. Jayachandran, J.; Srinivasan, H.; Mani, K.P. Molecular mechanism involved in epithelial to mesenchymal transition. Arch. Biochem. Biophys., 2021, 710, 108984. doi: 10.1016/j.abb.2021.108984 PMID: 34252392
  35. Kim, B.N.; Ahn, D.H.; Kang, N.; Yeo, C.D.; Kim, Y.K.; Lee, K.Y.; Kim, T.J.; Lee, S.H.; Park, M.S.; Yim, H.W.; Park, J.Y.; Park, C.K.; Kim, S.J. TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci. Rep., 2020, 10(1), 10597. doi: 10.1038/s41598-020-67325-7 PMID: 32606331
  36. Bai, F.; Zhang, L.H.; Liu, X.; Wang, C.; Zheng, C.; Sun, J.; Li, M.; Zhu, W.G.; Pei, X.H. GATA3 functions downstream of BRCA1 to suppress EMT in breast cancer. Theranostics, 2021, 11(17), 8218-8233. doi: 10.7150/thno.59280 PMID: 34373738
  37. Cao, Y.; Geng, J.; Wang, X.; Meng, Q.; Xu, S.; Lang, Y.; Zhou, Y.; Qi, L.; Wang, Z.; Wei, Z.; Yu, Y.; Jin, S.; Pan, B. RNA-binding motif protein 10 represses tumor progression through the Wnt/β- catenin pathway in lung adenocarcinoma. Int. J. Biol. Sci., 2022, 18(1), 124-139. doi: 10.7150/ijbs.63598 PMID: 34975322
  38. Ma, X.; Wang, B.; Wang, X.; Luo, Y.; Fan, W. NANOGP8 is the key regulator of stemness, EMT, Wnt pathway, chemoresistance, and other malignant phenotypes in gastric cancer cells. PLoS One, 2018, 13(4), e0192436. doi: 10.1371/journal.pone.0192436 PMID: 29689047
  39. Guo, H.; Peng, J.; Hu, J.; Chang, S.; Liu, H.; Luo, H.; Chen, X.; Tang, H.; Chen, Y. BAIAP2L2 promotes the proliferation, migration and invasion of osteosarcoma associated with the Wnt/β-catenin pathway. J. Bone Oncol., 2021, 31, 100393. doi: 10.1016/j.jbo.2021.100393 PMID: 34786330
  40. Yang, J.; Yang, Q.; Yu, J.; Li, X.; Yu, S.; Zhang, X. SPOCK1 promotes the proliferation, migration and invasion of glioma cells through PI3K/AKT and Wnt/β-catenin signaling pathways. Oncol. Rep., 2016, 35(6), 3566-3576. doi: 10.3892/or.2016.4757 PMID: 27108836

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Bentham Science Publishers, 2024