Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Cervical Cancer | Research

LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer

Authors: Zhengyan Cheng, Hongbo Wang, Zewei Yang, Jiaxu Li, Xing Chen

Published in: BMC Cancer | Issue 1/2023

Login to get access

Abstract

Background

The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells.

Methods

The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells.

Results

In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT.

Conclusion

LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.
Appendix
Available only for authorised users
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-Cancer J Clin. 2018;68(6):394–424.CrossRefPubMed
2.
Revathidevi S, Murugan AK, Nakaoka H, Inoue I, Munirajan AK. APOBEC: a molecular driver in Cervical cancer pathogenesis. Cancer Lett. 2021;496:104–16.CrossRefPubMed
3.
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Curr Oncol Rep. 2021;23(6):61.CrossRefPubMed
4.
5.
Yang M, Hu H, Wu S, Ding J, Yin B, Huang B, Li F, Guo X, Han L. EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of Cervical cancer via mir-5003-3p-dependent upregulation of OGN expression. J Exp Clin Canc Res. 2022;41(1):165.CrossRef
6.
Li Q, Zhou ZW, Duan W, Qian CY, Wang SN, Deng MS, Zi D, Wang JM, Mao CY, Song GB, et al. Inhibiting the redox function of APE1 suppresses Cervical cancer Metastasis via disengagement of ZEB1 from E-cadherin in EMT. J Exp Clin Canc Res. 2021;40(1):220.CrossRef
7.
Lüönd F, Sugiyama N, Bill R, Bornes L, Hager C, Tang F, Santacroce N, Beisel C, Ivanek R, Bürglin T, et al. Distinct contributions of partial and full EMT to Breast cancer malignancy. Dev Cell. 2021;56(23):3203–21.CrossRefPubMed
8.
Pastushenko I, Mauri F, Song YA-O, de Cock F, Meeusen B, Swedlund BA-O, Impens FA-O, Van Haver DA-O, Opitz M, Thery MA-O, et al. Fat1 deletion promotes hybrid EMT state, tumour stemness and Metastasis. Nature. 2021;589(7842):448–55.CrossRefPubMed
9.
Wu L, Han L, Zhou C, Wei W, Chen X, Yi H, Wu X, Bai X, Guo S, Yu Y, et al. TGF-β1-induced CK17 enhances cancer stem cell-like properties rather than EMT in promoting Cervical cancer Metastasis via the ERK1/2-MZF1 signaling pathway. FEBS J. 2017;284(18):3000–17.CrossRefPubMed
10.
Wang Q, Yen YT, Xie C, Liu FC, Liu Q, Wei J, Yu LX, Wang LF, Meng FY, Li RT, et al. Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits Cervical cancer cells and cancer stem cells. Drug Deliv. 2021;28(1):510–9.CrossRefPubMedPubMedCentral
11.
Kim L, Park SA, Park H, Kim H, Heo TH. Bazedoxifene, a GP130 inhibitor, modulates EMT signaling and exhibits antitumor effects in HPV-positive Cervical cancer. Int J Mol Sci. 2021;22(16):8693.CrossRefPubMedPubMedCentral
12.
Lei HW, Shi JB, Teng Y, Song CH, Zou LJ, Ye FX, Zhang HC. Baicalein modulates the radiosensitivity of Cervical cancer cells in vitro via miR-183 and the JAK2/STAT3 signaling pathway. Adv Clin Exp Med. 2021;30(7):727–36.CrossRefPubMed
13.
Bugter JM, Fenderico N, Maurice MM. Mutations and mechanisms of WNT pathway tumour suppressors in cancer. Nat Rev Cancer. 2021;21(1):5–21.CrossRefPubMed
14.
15.
16.
Li Q, Lai Q, He C, Fang Y, Yan Q, Zhang Y, Wang X, Gu C, Wang Y, Ye L, et al. RUNX1 promotes tumour Metastasis by activating the Wnt/beta-catenin signalling pathway and EMT in Colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):334.CrossRefPubMedPubMedCentral
17.
Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M, Tao Q, Xu H. Wnt signaling in Colorectal cancer: pathogenic role and therapeutic target. Mol Cancer. 2022;21(1):144.CrossRefPubMedPubMedCentral
18.
Li C, Zhou Y, Rychahou P, Weiss HL, Lee EY, Perry CL, Barrett TA, Wang Q, Evers BM. SIRT2 contributes to the regulation of intestinal cell proliferation and differentiation. Cell Mol Gastroenterol Hepatol. 2020;10(1):43–57.CrossRefPubMedPubMedCentral
19.
Zhang X, Kang Z, Li Q, Zhang J, Cheng S, Chang H, Wang S, Cao S, Li T, Li J, et al. Antigen-adjuvant effects of icariin in enhancing tumor-specific immunity in mastocytoma-bearing DBA/2J mice. Biomed Pharmacother. 2018;99:810–6.CrossRefPubMed
20.
Dong S, Guo X, Han F, He Z, Wang Y. Emerging role of natural products in cancer immunotherapy. Acta Pharm Sinica b, 12(3):1163–85.
21.
Suvilesh KN, Nussbaum YI, Radhakrishnan V, Manjunath Y, Avella DM, Staveley-O’Carroll KF, Kimchi ET, Chaudhuri AA, Shyu CR, Li G, et al. Tumorigenic circulating Tumor cells from xenograft mouse models of non-metastatic NSCLC patients reveal distinct single cell heterogeneity and drug responses. Mol Cancer. 2022;21(1):73.CrossRefPubMedPubMedCentral
22.
Small W, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN, et al. Cervical Cancer: A Global Health Crisis. Cancer-Am Cancer Soc. 2017;123(13):2404–12.
23.
Zhao S, Huang L, Basu P, Domingo EJ, Supakarapongkul W, Ling WY, Ocviyanti D, Rezhake R, Qiao Y, Tay EH, et al. Cervical cancer burden, status of implementation and challenges of Cervical cancer screening in Association of Southeast Asian Nations (ASEAN) countries. Cancer Lett. 2021;525:22–32.CrossRefPubMed
24.
Bandoh NOT, Katayama A, Takahara M, Katada A, Hayashi T, Harabuchi Y. HLA class I antigen and transporter associated with antigen processing downregulation in metastatic lesions of head and neck squamous cell carcinoma as a marker of poor prognosis. Oncol Rep. 2010;23(4):93–9.CrossRef
25.
Yang J, Liu W, Yan Z, Li C, Liu S, Yang X, Li Y, Shi L, Yao Y. Polymorphisms in transporter associated with antigen presenting are associated with cervical intraepithelial neoplasia and Cervical cancer in a Chinese Han population. HLA. 2021;98(1):23–36.CrossRefPubMed
26.
Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman R, O’Brien S, Yenerel MN, Illés A, Kay N, et al. Acalabrutinib versus Ibrutinib in previously treated chronic lymphocytic Leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39(31):3441–52.CrossRefPubMedPubMedCentral
27.
Geoffroy K, Araripe Saraiva B, Viens M, Béland D, Bourgeois-Daigneault MC. Increased expression of the immunoproteasome subunits PSMB8 and PSMB9 by cancer cells correlate with better outcomes for triple-negative breast cancers. Sci Rep, 13(1):2129.
28.
Liu W, Ma Q, Li C, Li Y, Liu S, Shi L, Yao Y. The association of TAP polymorphisms with non-small-cell Lung cancer in the Han Chinese population. Hum Immunol. 2021;82(12):917–22.CrossRefPubMed
29.
Palomar G, Dudek K, Migalska M, Arntzen JW, Ficetola GF, Jelić D, Jockusch E, Martínez-Solano I, Matsunami M, Shaffer HB, et al. Coevolution between MHC class I and Antigen-Processing genes in salamanders. Mol Biol Evol. 2021;38(11):5092–106.CrossRefPubMedPubMedCentral
30.
Cai YQ, Song YL, Cen DW, Zhang CQ, Mao SS, Ye XX, Xiong YR, Jiang PF, Chen J, Xue XY, et al. Novel ELISA for serodiagnosis of nasopharyngeal carcinoma based on a B cell epitope of Epstein-Barr virus latent membrane protein 2. Oncol Lett. 2018;16(4):4372–8.PubMedPubMedCentral
31.
Hwang SA-O, Kwon AY, Jeong JY, Kim S, Kang H, Park J, Kim JH, Han OJ, Lim SM, An HJ. Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell Lung cancer. Sci Rep. 2020;10(1):643.CrossRefPubMedPubMedCentral
32.
Shirazi F, Jones RJ, Singh R, Zou J, Kuiatse I, Berkova Z, Wang H, Lee HC, Hong S, Dick L, et al. Activating KRAS, NRAS, and BRAF mutants enhance proteasome capacity and reduce endoplasmic reticulum stress in Multiple Myeloma. Proc Natl Acad Sci USA. 2020;117(33):20004–14.CrossRefPubMedPubMedCentral
33.
34.
35.
Tang QA-O, Chen J, Di Z, Yuan W, Zhou Z, Liu Z, Han S, Liu Y, Ying G, Shu X, et al. TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in Colorectal cancer. J Exp Clin Canc Res. 2020;39(1):232.CrossRef
36.
He Y, Jiang X, Duan L, Xiong Q, Yuan Y, Liu P, Jiang L, Shen Q, Zhao S, Yang C, et al. LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell Lung cancer via activating wnt signaling pathway. Mol Cancer. 2021;20(1):156.CrossRefPubMedPubMedCentral
37.
Xu T, Zeng Y, Shi L, Yang Q, Chen Y, Wu G, Li G, Xu S. Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/beta-catenin signaling pathway in Cervical cancer. J Exp Clin Cancer Res. 2020;39(1):183.CrossRefPubMedPubMedCentral
Metadata
Title
LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer
Authors
Zhengyan Cheng
Hongbo Wang
Zewei Yang
Jiaxu Li
Xing Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11639-y

Other articles of this Issue 1/2023

BMC Cancer 1/2023 Go to the issue

Research

A novel cuproptosis-related gene signature to predict prognosis in Glioma

Research

A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis

Research

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study

Research

DCLRE1B promotes tumor progression and predicts immunotherapy response through METTL3-mediated m6A modification in pancreatic cancer

Research

PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

Study protocol

Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits