Expression of SORT1 in Gastric Cancer Tissue and Its Effect on Gastric Cancer Cell Biology

Linyu XIAO; Ting DUAN; Yongsheng XIA; Yue CHEN; Xingzhou YAN; Jianguo HU

doi:10.3881/j.issn.1000-503X.16238

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Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (3) : 343-353. DOI: 10.3881/j.issn.1000-503X.16238

Original Articles

Expression of SORT1 in Gastric Cancer Tissue and Its Effect on Gastric Cancer Cell Biology

Linyu XIAO ¹ ,
Ting DUAN ² ,
Yongsheng XIA ³ ,
Yue CHEN ¹ ,
Xingzhou YAN ¹ ,
Jianguo HU ⁴^,⁵

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Abstract

Objective To investigate the expression of SORT1 in the gastric cancer tissue and analyze its relationship with clinical prognosis of patients as well as the pathways and mechanisms involved in gastric cancer progression.Methods The Gene Expression Profiling Interaction Analysis database,Western blot,and immunohistochemistry were employed to predict and analyze the expression of SORT1 in the gastric cancer and the adjacent tissue.The clinical case information of 109 patients who underwent radical surgery for gastric cancer in the First Affiliated Hospital of Bengbu Medical University from April 2015 to April 2017 was collected to analyze the relationship of SORT1 with the clinicopathological parameters and prognosis of the patients.Cell proliferation was detected by the CCK-8 assay and colony formation assay,while cell migration and invasion were assessed by the scratch assay and Transwell assay,respectively.Western blot was employed to determine the expression of proteins related to epithelial-mesenchymal transition(EMT)in gastric cancer cells,followed by further analysis on molecular mechanism through which SORT1 regulates EMT in gastric cancer cells.Results Western blot and immunocytochemistry results showed that SORT1 was highly expressed in the gastric cancer tissue(P=0.003,P<0.001),which was positively correlated with malignant progression of tumors(all P<0.05).The Kaplan-Meier survival analysis revealed shortened postoperative survival periods for the patients with high expression of SORT1(P<0.001).The Cox regression model indicated that SORT1 expression was an independent risk factor affecting the 5-year survival rate after surgery for gastric cancer patients(P<0.001).Up-regulation of SORT1 expression promoted the proliferation,migration,invasion,and EMT of gastric cancer cells(all P<0.05),while down-regulation of SORT1 showed the opposite effects(all P<0.05).Western blot results showed that high expression of SORT1 promoted the expression of β-catenin,cyclin D1,and c-Myc(all P<0.05).Moreover,in vitro use of the Wnt/β-catenin pathway inhibitor(XAV939)effectively suppressed the EMT enhancement caused by high expression of SORT1 in gastric cancer cells(all P<0.05).Conclusions SORT1 is highly expressed in gastric cancer and affects patients’ postoperative survival periods.It is involved in the proliferation,migration,and invasion of gastric cancer cells and may promote the EMT of gastric cancer cells by activating the Wnt/β-catenin pathway.

Key words

gastric cancer / SORT1 / prognosis / epithelial-mesenchymal transition, Wnt/β-catenin pathway

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Linyu XIAO , Ting DUAN , Yongsheng XIA , et al . Expression of SORT1 in Gastric Cancer Tissue and Its Effect on Gastric Cancer Cell Biology[J]. Acta Academiae Medicinae Sinicae. 2025, 47(3): 343-353 https://doi.org/10.3881/j.issn.1000-503X.16238

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	Catalano V, Labianca R, Beretta GD, et al. Gastric cancer[J]. Crit Rev Oncol Hematol, 2009, 71(2):127-164.DOI:10.1016/j.critrevonc.2009.01.004. Cited in this article [1]

[2]	Lin JT. Screening of gastric cancer:who,when,and how[J]. Clin Gastroenterol Hepatol, 2014, 12(1):135-138.DOI:10.1016/j.cgh.2013.09.064. Cited in this article [1]

[3]	Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15:a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5):e555-e567.DOI:10.1016/S2214-109X(18)30127-X. Cited in this article [1]

[4]	Kashyap D, Baral B, Jakhmola S, et al. Helicobacter pylori and Epstein-Barr virus coinfection stimulates aggressiveness in gastric cancer through the regulation of gankyrin[J]. Sphere, 2021, 6(5):e0075121.DOI:10.1128/mSphere.00751-21. Cited in this article [1]

[5]	Meng D, Li D. Ubiquitin-specific protease 1 overexpression indicates poor prognosis and promotes proliferation,migration,and invasion of gastric cancer cells[J]. Tissue Cell, 2022,74:101723.DOI:10.1016/j.tice.2021.101723. Cited in this article [1]

[6]	Ouyang S, Jia B, Xie W, et al. Mechanism underlying the regulation of Sortilin expression and its trafficking function[J]. J Cell Physiol, 2020, 235(12):8958-8971.DOI:10.1002/jcp.29818. Cited in this article [1]

[7]	Ghaemimanesh F, Mehravar M, Milani S, et al. The multifaceted role of Sortilin/neurotensin receptor 3 in human cancer development[J]. J Cell Physiol, 2021, 236(9):6271-6281.DOI:10.1002/jcp.30344. Cited in this article [1]

[8]	Blondy S, Talbot H, Saada S, et al. Overexpression of Sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer[J]. J Cell Mol Med, 2021, 25(1):47-60.DOI:10.1111/jcmm.15752. Cited in this article [2]

[9]	Rhost S, Hughes É, Harrison H, et al. Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion[J]. Breast Cancer Res, 2018, 20(1):137.DOI:10.1186/s13058-018-1060-5. Cited in this article [2]

[10]	Zhuang W, Zhang W, Xie L, et al. Generation and characterization of SORT1-targeted antibody-drug conjugate for the treatment of SORT1-positive breast tumor[J]. Int J Mol Sci, 2023, 24(24):17631.DOI:10.3390/ijms242417631. Cited in this article [1]

[11]	Gao Y, Li Y, Song Z, et al. Sortilin 1 promotes hepatocellular carcinoma cell proliferation and migration by regulating immune cell infiltration[J]. J Oncol, 2022,2022:6509028.DOI:10.1155/2022/6509028. Cited in this article [2]

[12]	Li Y, Zhao Y, Li Y, et al. Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway[J]. J Physiol Biochem, 2021, 77(1):93-104.DOI:10.1007/s13105-020-00780-y. Cited in this article [1]

[13]	Zhang XM, Liu ZL, Qiu B, et al. Downregulation of EVI1 expression inhibits cell proliferation and induces apoptosis in hilar cholangiocarcinoma via the PTEN/AKT signalling pathway[J]. J Cancer, 2020, 11(6):1412-1423.DOI:10.7150/jca.31903. Cited in this article [1]

[14]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China,2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.DOI:10.3322/caac.21338. Cited in this article [1]

[15]	Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer[J]. Lancet, 2020, 396(10251):635-648.DOI:10.1016/S0140-6736(20)31288-5. Cited in this article [1]

[16]	Wilson CM, Naves T, Saada S, et al. The implications of Sortilin/vps10p domain receptors in neurological and human diseases[J]. CNS Neurol Disord Drug Targets, 2014, 13(8):1354-1365.DOI:10.2174/1871527313666141023151642. Cited in this article [1]

[17]	Yang W, Wu PF, Ma JX, et al. Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3β/β-catenin/twist pathway[J]. Cell Death Dis, 2019, 10(3):208.DOI:10.1038/s41419-019-1449-9. Cited in this article [1]

[18]	Al-Akhrass H, Naves T, Vincent F, et al. Sortilin limits EGFR signaling by promoting its internalization in lung cancer[J]. Nat Commun, 2017, 8(1):1182.DOI:10.1038/s41467-017-01172-5. Cited in this article [1]

[19]	Marsland M, Dowdell A, Faulkner S, et al. The membrane protein Sortilin is a potential biomarker and target for glioblastoma[J]. Cancers(Basel), 2023, 15(9):2514.DOI:10.3390/cancers15092514. Cited in this article [1]

[20]	Martini C, Logan JM, Sorvina A, et al. Aberrant protein expression of Appl1,Sortilin and Syndecan-1 during the biological progression of prostate cancer[J]. Pathology, 2023, 55(1):40-51.DOI:10.1016/j.pathol.2022.08.001. Cited in this article [1]

[21]	Mazella J. Deciphering mechanisms of action of Sortilin/neurotensin receptor-3 in the proliferation regulation of colorectal and other cancers[J]. Int J Mol Sci, 2022, 23(19):11888.DOI:10.3390/ijms231911888. Cited in this article [1]

[22]	刘志娴, 魏尔清, 卢韵碧. 上皮-间质转化在肿瘤发生发展中的作用研究进展[J]. 浙江大学学报(医学版), 2015, 44(2):211-216.DOI:10.3785/j.issn.1008-9292.2015.03.015 Cited in this article [1]

[23]	Iwatsuki M, Mimori K, Yokobori T, et al. Epithelial-mesenchymal transition in cancer development and its clinical significance[J]. Cancer Sci, 2010, 101(2):293-299.DOI:10.1111/j.1349-7006.2009.01419.x. Cited in this article [1]

[24]	Hayat R, Manzoor M, Hussain A. Wnt signaling pathway:a comprehensive review[J]. Cell Biol Int, 2022, 46(6):863-877.DOI:10.1002/cbin.11797. Cited in this article [1]

[25]	Koushyar S, Powell AG, Vincan E, et al. Targeting Wnt signaling for the treatment of gastric cancer[J]. Int J Mol Sci, 2020, 21(11):3927.DOI:10.3390/ijms21113927. Cited in this article [1]

[26]	Xue W, Yang L, Chen C, et al. Wnt/β-catenin-driven EMT regulation in human cancers[J]. Cell Mol Life Sci, 2024, 81(1):79.DOI:10.1007/s00018-023-05099-7. Cited in this article [1]

[27]	Tian S, Peng P, Li J, et al. SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway[J]. Aging(Albany NY), 2020, 12(4):3574-3593.DOI:10.18632/aging.102831. Cited in this article [1]

[28]	Yang S, Liu Y, Li MY, et al. FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer[J]. Mol Cancer, 2017, 16(1):124.DOI:10.1186/s12943-017-0700-1. Cited in this article [1]

[29]	Gong J, Wang Y, Shu C. LncRNA CHRF promotes cell invasion and migration via EMT in gastric cancer[J]. Eur Rev Med Pharmacol Sci, 2020, 24(3):1168-1176.DOI:10.26355/eurrev_202002_20168. Cited in this article [1]

[30]	Jia S, Qu T, Wang X, et al. KIAA1199 promotes migration and invasion by Wnt/β-catenin pathway and MMPs mediated EMT progression and serves as a poor prognosis marker in gastric cancer[J]. PLoS One, 2017, 12(4):e0175058.DOI:10.1371/journal.pone.0175058. Cited in this article [1]