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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Research Article

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

Author(s): Xiaoping Cai, Yuankai Lv, Jiongwei Pan, Zhuo Cao, Junzhi Zhang, Yuling Li and Hao Zheng*

Volume 25, Issue 5, 2024

Published on: 23 January, 2024

Page: [386 - 393] Pages: 8

DOI: 10.2174/0113892037273375231204080906

Price: $65

Abstract

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.

Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.3892/or.2016.4757] [PMID: 27108836]

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