Journal of Shanghai Jiao Tong University (Medical Science) >

2024 , Vol. 44 >Issue 11: 1335 - 1346

DOI: https://doi.org/10.3969/j.issn.1674-8115.2024.11.001

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Promotive effect of cancer-testis antigen CT57 on proliferation, invasion, migration and epithelial-mesenchymal transition of liver cancer cells

  • Lange LUO ,
  • Chao ZHENG ,
  • Ming LEI
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  • Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
ZHENG Chao, E-mail: zhengchao@shsmu.edu.cn.
LEI Ming, E-mail: leim@shsmu.edu.cn

Received date: 2024-02-21

  Accepted date: 2024-04-23

  Online published: 2024-11-28

Supported by

National Key Research and Development Program of China(2018YFA0107004)

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Abstract

Objective ·To investigate the effect of cancer-testis antigen family member CT57 on proliferation, migration and invasion of the human liver cancer cells and tumorigenesis in nude mice, and the possible mechanism. Methods ·Bioinformatics methods were used to analyze the differential expression of CT57 in several cancer tissues and normal tissues, and its effect on the prognosis of liver cancer patients. Lentiviral vectors were used to establish liver cancer cell lines with stable knockdown and overexpression of CT57, which were confirmed by Western blotting. CCK-8 cell proliferation assay, soft agar colony formation assay and cell cycle experiment were used to detect the effect of CT57 on the proliferation and colony formation ability of liver cancer cells. Wound healing and Transwell assays were used to detect the effect of CT57 on the migration and invasion of liver cancer cells, and the expression of epithelial-mesenchymal transition (EMT) markers was detected by quantitative real-time PCR (qRT-PCR). To explore the effect of CT57 on liver cancer cells in vivo, CT57 knockdown liver cancer cells (experimental group) and control liver cancer cells (control group) were used to conduct subcutaneous tumor formation experiments in nude mice. Results ·Bioinformatics analysis of multiple tumors and corresponding normal tissues in The Cancer Genome Atlas Program (TCGA) database showed that CT57 was highly expressed in most tumor tissues, including liver cancer, and the expression level of CT57 was significantly correlated with the prognosis of liver cancer patients. Cell proliferation assay, soft agar colony formation assay, and cell cycle experiment showed that knockdown of CT57 inhibited the proliferation and colony formation of liver cancer cells and led to cell cycle arrest. In wound healing and Transwell assays, knockdown of CT57 inhibited the invasion and migration of liver cancer cells, while overexpression of CT57 promoted it. The results of qRT-PCR indicated that overexpression of CT57 resulted in downregulation of epithelial cell markers ECAD (E-cadherin) and OCLN (occludin), and upregulation of mesenchymal cell markers VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), and MMP2 (matrix metallopeptidase 2). In the in vivo experiments, knockdown of CT57 significantly reduced the tumor formation rate of liver cancer cells, tumor volume, and tumor weight in nude mice. Conclusion ·Knockdown of CT57 leads to cell cycle arrest, thereby inhibiting the proliferation of liver cancer cell and subcutaneous tumorigenesis in nude mice; CT57 promotes the invasion, migration and EMT of liver cancer cells.

Key words： cancer-testis antigen; liver cancer; cell proliferation; invasion; migration; epithelial-mesenchymal transition (EMT)

Cite this article

Lange LUO , Chao ZHENG , Ming LEI . Promotive effect of cancer-testis antigen CT57 on proliferation, invasion, migration and epithelial-mesenchymal transition of liver cancer cells[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024 , 44(11) : 1335 -1346 . DOI: 10.3969/j.issn.1674-8115.2024.11.001

References

1 LLOVET J M, KELLEY R K, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7(1): 6.
2 TANG A, HALLOUCH O, CHERNYAK V, et al. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis[J]. Abdom Radiol, 2018, 43(1): 13-25.
3 CHENG A L, KANG Y K, CHEN Z D, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase Ⅲ randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2009, 10(1): 25-34.
4 KIRKIN A F, DZHANDZHUGAZYAN K N, ZEUTHEN J. Cancer/testis antigens: structural and immunobiological properties[J]. Cancer Invest, 2002, 20(2): 222-236.
5 ALMEIDA L G, SAKABE N J, DEOLIVEIRA A R, et al. CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens[J]. Nucleic Acids Res, 2009, 37(Database issue): D816-D819.
6 SIMPSON A J, CABALLERO O L, JUNGBLUTH A, et al. Cancer/testis antigens, gametogenesis and cancer[J]. Nat Rev Cancer, 2005, 5(8): 615-625.
7 CHENG W, LI H L, XI S Y, et al. Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma[J]. Nat Commun, 2021, 12(1): 7142.
8 KIM M C, BORCHERDING N, AHMED K K, et al. CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells[J]. Nat Commun, 2021, 12(1): 5764.
9 DONG X Y, YANG X A, WANG Y D, et al. Zinc-finger protein ZNF165 is a novel cancer-testis antigen capable of eliciting antibody response in hepatocellular carcinoma patients[J]. Br J Cancer, 2004, 91(8): 1566-1570.
10 CHEN Y T, SCANLAN M J, VENDITTI C A, et al. Identification of cancer/testis-antigen genes by massively parallel signature sequencing[J]. Proc Natl Acad Sci U S A, 2005, 102(22): 7940-7945.
11 FAN S X, YAN S, YANG Y, et al. Actin-like protein 8 promotes the progression of triple-negative breast cancer via activating PI3K/AKT/mTOR pathway[J]. Onco Targets Ther, 2021, 14: 2463-2473.
12 WANG L F, XING X L, TIAN H, et al. Actin-like protein 8, a member of cancer/testis antigens, supports the aggressive development of oral squamous cell carcinoma cells via activating cell cycle signaling[J]. Tissue Cell, 2022, 75: 101708.
13 MA S W, WANG X W, ZHANG Z R, et al. Actin-like protein 8 promotes cell proliferation, colony-formation, proangiogenesis, migration and invasion in lung adenocarcinoma cells[J]. Thorac Cancer, 2020, 11(3): 526-536.
14 YANG P, QIAO Y N, MENG M, et al. Cancer/testis antigens as biomarker and target for the diagnosis, prognosis, and therapy of lung cancer[J]. Front Oncol, 2022, 12: 864159.
15 FREITAS M, MALHEIROS S, STáVALE J N, et al. Expression of cancer/testis antigens is correlated with improved survival in glioblastoma[J]. Oncotarget, 2013, 4(4): 636-646.
16 LI B, ZHU J, MENG L. High expression of ACTL8 is poor prognosis and accelerates cell progression in head and neck squamous cell carcinoma[J]. Mol Med Rep, 2019, 19(2): 877-884.
17 MA S W, QIANG G L, SHAO W P, et al. Knockdown of actin-like 8 inhibits cell proliferation by regulating FOXM1, STMN1, PLK1, and BIRC5 in lung adenocarcinoma A549 cells[J]. Transl Cancer Res, 2019, 8(5): 1975-1984.
18 HAN Q, SUN M L, LIU W S, et al. Upregulated expression of ACTL8 contributes to invasion and metastasis and indicates poor prognosis in colorectal cancer[J]. Onco Targets Ther, 2019, 12: 1749-1763.
19 HUBER B E, THORGEIRSSON S S. Analysis of c-myc expression in a human hepatoma cell line[J]. Cancer Res, 1987, 47(13): 3414-3420.
20 CHEN Y P, CHAN A T C, LE Q T, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80.
21 HANAHAN D. Hallmarks of cancer: new dimensions[J]. Cancer Discov, 2022, 12(1): 31-46.
22 SERRANO-GOMEZ S J, MAZIVEYI M, ALAHARI S K. Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications[J]. Mol Cancer, 2016, 15: 18.
23 SMITH B N, BHOWMICK N A. Role of EMT in metastasis and therapy resistance[J]. J Clin Med, 2016, 5(2): 17.
24 YE H, KELLY T F, SAMADANI U, et al. Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues[J]. Mol Cell Biol, 1997, 17(3): 1626-1641.
25 KORVER W, ROOSE J, HEINEN K, et al. The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization[J]. Genomics, 1997, 46(3): 435-442.
26 MENG F D, WEI J C, QU K, et al. FoxM1 overexpression promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma[J]. World J Gastroenterol, 2015, 21(1): 196-213.
27 YU M, TANG Z, MENG F D, et al. Elevated expression of FoxM1 promotes the tumor cell proliferation in hepatocellular carcinoma[J]. Tumour Biol, 2016, 37(1): 1289-1297.
28 BALLI D, USTIYAN V, ZHANG Y F, et al. Foxm1 transcription factor is required for lung fibrosis and epithelial-to-mesenchymal transition[J]. EMBO J, 2013, 32(2): 231-244.
29 WANG C R, WANG X J, SU Z J, et al. MiR-25 promotes hepatocellular carcinoma cell growth, migration and invasion by inhibiting RhoGDI1[J]. Oncotarget, 2015, 6(34): 36231-36244.
30 ZHANG N, WEI P, GONG A H, et al. FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis[J]. Cancer Cell, 2011, 20(4): 427-442.
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