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GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells

  • Authors:
    • Shan-Shan Li
    • Dong-Mei Chen
    • Lu-Biao Chen
    • Huan Wei
    • Jia-Liang Wang
    • Jian Xiao
    • Yue-Hua Huang
    • Yi-Fan Lian
  • View Affiliations / Copyright

    Affiliations: Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 454
    |
    Published online on: April 15, 2021
       https://doi.org/10.3892/mmr.2021.12093
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Abstract

Snail family transcriptional repressor 1 (SNAIL1) is a master inducer of the epithelial‑to‑mesenchymal transition (EMT) process, contributing to tumor metastasis and recurrence. Our previous study reported that G2 and S phase‑expressed‑1 (GTSE1) served a role in regulating SNAIL1 expression in hepatocellular carcinoma (HCC). However, the underlying mechanism remains unknown. Therefore, the present study aimed to reveal the regulatory mechanism of GTSE1 on SNAIL1 expression using in vitro assays performed in HCC cell models. It was demonstrated that endogenous SNAIL1 expression was downregulated and upregulated by GTSE1 overexpression or small interfering RNA‑mediated knockdown, respectively. Via cycloheximide chase experiments, it was identified that GTSE1 overexpression increased the protein turnover of SNAIL1, while knockdown of GTSE1 reduced its degradation rate. Furthermore, it was demonstrated that GTSE1 overexpression induced the cytoplasmic expression of SNAIL1 using immunofluorescence and subcellular fractionation methods. The nuclear export inhibitor leptomycin B was able to decrease the cytoplasmic retention of SNAIL1 caused by GTSE1 overexpression. In addition, TGF‑βI treatment increased both the mRNA and protein expression levels of GTSE1, and decreased the protein expression level of SNAIL1 without affecting its mRNA transcription in Huh7 cells. It was also found that TGF‑β signaling could upregulate the transcription of GTSE1 expression by transactivating the Smad binding elements in the GTSE1 promoter. Moreover, the TGF‑βI‑induced decrease in SNAIL1 protein expression was GTSE1‑dependent in Huh7 cells. In conclusion, the current study provides a novel mechanism via which GTSE1 affects the stability of SNAIL1 by regulating its subcellular localization in HCC cells.
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1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Bruix J, Reig M and Sherman M: Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 150:835–853. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Forner A, Reig M and Bruix J: Hepatocellular carcinoma. Lancet. 391:1301–1314. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Nieto MA: The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol. 3:155–166. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Domínguez D, Montserrat-Sentís B, Virgós-Soler A, Guaita S, Grueso J, Porta M, Puig I, Baulida J, Francí C and García de Herreros A: Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor. Mol Cell Biol. 23:5078–5089. 2003. View Article : Google Scholar

6 

Wang Y, Shi J, Chai K, Ying X and Zhou BP: The role of snail in EMT and tumorigenesis. Curr Cancer Drug Targets. 13:963–972. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY and Bapat SA: Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 27:2059–2068. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, Notorfrancesco KL, Cardiff RD and Chodosh LA: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 8:197–209. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Vincent T, Neve EP, Johnson JR, Kukalev A, Rojo F, Albanell J, Pietras K, Virtanen I, Philipson L, Leopold PL, et al: A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol. 11:943–950. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Ruan HB, Nie Y and Yang X: Regulation of protein degradation by O-GlcNAcylation: Crosstalk with ubiquitination. Mol Cell Proteomics. 12:3489–3497. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M and Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 6:931–940. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Muqbil I, Wu J, Aboukameel A, Mohammad RM and Azmi AS: Snail nuclear transport: The gateways regulating epithelial-to-mesenchymal transition? Semin Cancer Biol. 27:39–45. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Wu X, Wang H, Lian Y, Chen L, Gu L, Wang J and Huang Y, Deng M, Gao Z and Huang Y: GTSE1 promotes cell migration and invasion by regulating EMT in hepatocellular carcinoma and is associated with poor prognosis. Sci Rep. 7:51292017. View Article : Google Scholar : PubMed/NCBI

14 

Monte M, Benetti R, Collavin L, Marchionni L, Del Sal G and Schneider C: hGTSE-1 expression stimulates cytoplasmic localization of p53. J Biol Chem. 279:11744–11752. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Scolz M, Widlund PO, Piazza S, Bublik DR, Reber S, Peche LY, Ciani Y, Hubner N, Isokane M, Monte M, et al: GTSE1 is a microtubule plus-end tracking protein that regulates EB1-dependent cell migration. PLoS One. 7:e512592012. View Article : Google Scholar : PubMed/NCBI

16 

Subhash VV, Tan SH, Tan WL, Yeo MS, Xie C, Wong FY, Kiat ZY, Lim R and Yong WP: GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells. BMC Cancer. 15:5502015. View Article : Google Scholar : PubMed/NCBI

17 

Lian YF, Huang YL, Zhang YJ, Chen DM, Wang JL, Wei H, Bi YH, Jiang ZW, Li P, Chen MS, et al: CACYBP enhances cytoplasmic retention of P27Kip1 to promote hepatocellular carcinoma progression in the absence of RNF41 mediated degradation. Theranostics. 9:8392–8408. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Chen J, Ding ZY, Li S, Liu S, Xiao C, Li Z, Zhang BX, Chen XP and Yang X: Targeting transforming growth factor-β signaling for enhanced cancer chemotherapy. Theranostics. 11:1345–1363. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Martin-Malpartida P, Batet M, Kaczmarska Z, Freier R, Gomes T, Aragón E, Zou Y, Wang Q, Xi Q, Ruiz L, et al: Structural basis for genome wide recognition of 5-bp GC motifs by SMAD transcription factors. Nat Commun. 8:20702017. View Article : Google Scholar : PubMed/NCBI

21 

Yang Z, Rayala S, Nguyen D, Vadlamudi RK, Chen S and Kumar R: Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions. Cancer Res. 65:3179–3184. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Zhang K, Rodriguez-Aznar E, Yabuta N, Owen RJ, Mingot JM, Nojima H, Nieto MA and Longmore GD: Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. EMBO J. 31:29–43. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Monte M, Benetti R, Buscemi G, Sandy P, Del Sal G and Schneider C: The cell cycle-regulated protein human GTSE-1 controls DNA damage-induced apoptosis by affecting p53 function. J Biol Chem. 278:30356–30364. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Liu XS, Li H, Song B and Liu X: Polo-like kinase 1 phosphorylation of G2 and S-phase-expressed 1 protein is essential for p53 inactivation during G2 checkpoint recovery. EMBO Rep. 11:626–632. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Bierie B and Moses HL: Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 6:506–520. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Massagué J: TGFβ signalling in context. Nat Rev Mol Cell Biol. 13:616–630. 2012. View Article : Google Scholar

27 

Moon H, Ju HL, Chung SI, Cho KJ, Eun JW, Nam SW, Han KH, Calvisi DF and Ro SW: Transforming growth factor-β promotes liver tumorigenesis in mice via up-regulation of snail. Gastroenterology. 153:1378–1391.e6. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Kawai T, Yasuchika K, Ishii T, Miyauchi Y, Kojima H, Yamaoka R, Katayama H, Yoshitoshi EY, Ogiso S, Kita S, et al: SOX9 is a novel cancer stem cell marker surrogated by osteopontin in human hepatocellular carcinoma. Sci Rep. 6:304892016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li S, Chen D, Chen L, Wei H, Wang J, Xiao J, Huang Y and Lian Y: GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells. Mol Med Rep 23: 454, 2021.
APA
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J. ... Lian, Y. (2021). GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells. Molecular Medicine Reports, 23, 454. https://doi.org/10.3892/mmr.2021.12093
MLA
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J., Huang, Y., Lian, Y."GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells". Molecular Medicine Reports 23.6 (2021): 454.
Chicago
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J., Huang, Y., Lian, Y."GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells". Molecular Medicine Reports 23, no. 6 (2021): 454. https://doi.org/10.3892/mmr.2021.12093
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Chen D, Chen L, Wei H, Wang J, Xiao J, Huang Y and Lian Y: GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells. Mol Med Rep 23: 454, 2021.
APA
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J. ... Lian, Y. (2021). GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells. Molecular Medicine Reports, 23, 454. https://doi.org/10.3892/mmr.2021.12093
MLA
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J., Huang, Y., Lian, Y."GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells". Molecular Medicine Reports 23.6 (2021): 454.
Chicago
Li, S., Chen, D., Chen, L., Wei, H., Wang, J., Xiao, J., Huang, Y., Lian, Y."GTSE1 promotes SNAIL1 degradation by facilitating its nuclear export in hepatocellular carcin oma cells". Molecular Medicine Reports 23, no. 6 (2021): 454. https://doi.org/10.3892/mmr.2021.12093
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