Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/β-catenin Signaling Pathway

Author(s): Mengqi Zhu, Xinxin Zhang, Kaiji Gao, Lingmei Zhang, Xiaojia Feng, Hui Wang, Jing Li and Jianguang Jia*

Volume 27, Issue 4, 2024

Published on: 22 May, 2023

Page: [611 - 620] Pages: 10

DOI: 10.2174/1386207326666230426112941

Price: $65

conference banner
Abstract

Background: Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown.

Methods: SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/β- catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice.

Results: This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, β-catenin, phosphorylated GSK-3β, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed.

Conclusion: SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.

« Previous Next »
Graphical Abstract

[1]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[2]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; 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.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[3]
Rawla, P.; Barsouk, A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz. Gastroenterol., 2019, 14(1), 26-38.
[http://dx.doi.org/10.5114/pg.2018.80001] [PMID: 30944675]
[4]
Olefson, S.; Moss, S.F. Obesity and related risk factors in gastric cardia adenocarcinoma. Gastric Cancer, 2015, 18(1), 23-32.
[http://dx.doi.org/10.1007/s10120-014-0425-4] [PMID: 25209115]
[5]
Jia, J.; Zhang, X.; Zhan, D.; Li, J.; Li, Z.; Li, H.; Qian, J. LncRNA H19 interacted with miR‐130a‐3p and miR‐17‐5p to modify radio‐resistance and chemo‐sensitivity of cardiac carcinoma cells. Cancer Med., 2019, 8(4), 1604-1618.
[http://dx.doi.org/10.1002/cam4.1860] [PMID: 30843379]
[6]
Xu, H.; Zhang, L.; Miao, J.; Liu, S.; Liu, H.; Jia, T.; Zhang, Q. Patterns of recurrence in adenocarcinoma of the esophagogastric junction: A retrospective study. World J. Surg. Oncol., 2020, 18(1), 144.
[http://dx.doi.org/10.1186/s12957-020-01917-5] [PMID: 32593312]
[7]
Cao, J.; Yang, T.; Wang, G.; Zhang, H.; You, Y.; Chen, J.; Yang, J.; Yang, W. Analysis of the clinicopathological features and prognostic factors in 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction. Surg. Oncol., 2018, 27(3), 556-562.
[http://dx.doi.org/10.1016/j.suronc.2018.07.008] [PMID: 30217319]
[8]
Ajani, J.A.; D’Amico, T.A.; Bentrem, D.J.; Chao, J.; Corvera, C.; Das, P.; Denlinger, C.S.; Enzinger, P.C.; Fanta, P.; Farjah, F.; Gerdes, H.; Gibson, M.; Glasgow, R.E.; Hayman, J.A.; Hochwald, S.; Hofstetter, W.L.; Ilson, D.H.; Jaroszewski, D.; Johung, K.L.; Keswani, R.N.; Kleinberg, L.R.; Leong, S.; Ly, Q.P.; Matkowskyj, K.A.; McNamara, M.; Mulcahy, M.F.; Paluri, R.K.; Park, H.; Perry, K.A.; Pimiento, J.; Poultsides, G.A.; Roses, R.; Strong, V.E.; Wiesner, G.; Willett, C.G.; Wright, C.D.; McMillian, N.R.; Pluchino, L.A. Esophageal and esophagogastric junction cancers, version 2.2019, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2019, 17(7), 855-883.
[http://dx.doi.org/10.6004/jnccn.2019.0033] [PMID: 31319389]
[9]
Ma, R.; Yang, F.; Huang, D.; Zheng, M.; Wang, Y. The prognostic value of the expression of SMC4 mRNA in breast cancer. Dis. Markers, 2019, 2019, 1-7.
[http://dx.doi.org/10.1155/2019/2183057] [PMID: 31871499]
[10]
Peng, L.; Tang, Y.; Zhang, Y.; Guo, S.; Peng, L.; Ye, L.; Wang, Y.; Jiang, Y. Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia. Leuk. Lymphoma, 2018, 59(10), 2423-2430.
[http://dx.doi.org/10.1080/10428194.2017.1387906] [PMID: 29043883]
[11]
Zhou, B.; Yuan, T.; Liu, M.; Liu, H.; Xie, J.; Shen, Y.; Chen, P. Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer. Oncol. Rep., 2012, 28(4), 1263-1268.
[http://dx.doi.org/10.3892/or.2012.1929] [PMID: 22842912]
[12]
Feng, X.D.; Song, Q.; Li, C.W.; Chen, J.; Tang, H.M.; Peng, Z.H.; Wang, X.C. Structural maintenance of chromosomes 4 is a predictor of survival and a novel therapeutic target in colorectal cancer. Asian Pac. J. Cancer Prev., 2014, 15(21), 9459-9465.
[http://dx.doi.org/10.7314/APJCP.2014.15.21.9459] [PMID: 25422241]
[13]
Zhang, C.; Kuang, M.; Li, M.; Feng, L.; Zhang, K.; Cheng, S. SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression. Sci. Rep., 2016, 6(1), 34508.
[http://dx.doi.org/10.1038/srep34508] [PMID: 27687868]
[14]
Jiang, L.; Zhou, J.; Zhong, D.; Zhou, Y.; Zhang, W.; Wu, W.; Zhao, Z.; Wang, W.; Xu, W.; He, L.; Ma, Y.; Hu, Y.; Zhang, W.; Li, J. Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells. Oncogenesis, 2017, 6(3), e301.
[http://dx.doi.org/10.1038/oncsis.2017.8] [PMID: 28287612]
[15]
Abdi, E.; Latifi-Navid, S.; Zahri, S.; Yazdanbod, A.; Pourfarzi, F. Risk factors predisposing to cardia gastric adenocarcinoma: Insights and new perspectives. Cancer Med., 2019, 8(13), 6114-6126.
[http://dx.doi.org/10.1002/cam4.2497] [PMID: 31448582]
[16]
Chevallay, M.; Bollschweiler, E.; Chandramohan, S.M.; Schmidt, T.; Koch, O.; Demanzoni, G.; Mönig, S.; Allum, W. Cancer of the gastroesophageal junction: A diagnosis, classification, and management review. Ann. N. Y. Acad. Sci., 2018, 1434(1), 132-138.
[http://dx.doi.org/10.1111/nyas.13954] [PMID: 30138540]
[17]
Chen, Y.; Huang, F. Deng; Yuan, X.; Tao, Q.; Wang, T.; Li, D.; Fan, Y.; Peng, Q.; Tang, D. HIF-1-miR-219-SMC4 regulatory pathway promoting proliferation and migration of HCC under hypoxic condition. BioMed Res. Int., 2019, 2019, 1-9.
[http://dx.doi.org/10.1155/2019/8983704] [PMID: 31828143]
[18]
Zhou, J.; Wu, G.; Tong, Z.; Sun, J.; Su, J.; Cao, Z.; Luo, Y.; Wang, W. Prognostic relevance of SMC family gene expression in human sarcoma. Aging, 2021, 13(1), 1473-1487.
[http://dx.doi.org/10.18632/aging.202455] [PMID: 33460400]
[19]
Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol., 2019, 20(2), 69-84.
[http://dx.doi.org/10.1038/s41580-018-0080-4] [PMID: 30459476]
[20]
Santamaria, P.G.; Moreno-Bueno, G.; Portillo, F.; Cano, A. EMT: Present and future in clinical oncology. Mol. Oncol., 2017, 11(7), 718-738.
[http://dx.doi.org/10.1002/1878-0261.12091] [PMID: 28590039]
[21]
Zhang, Y.; Weinberg, R.A. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front. Med., 2018, 12(4), 361-373.
[http://dx.doi.org/10.1007/s11684-018-0656-6] [PMID: 30043221]
[22]
Zhang, X.; Zhu, M.; Wang, H.; Song, Z.; Zhan, D.; Cao, W.; Han, Y.; Jia, J. Overexpression of NCAPG inhibits cardia adenocarcinoma apoptosis and promotes epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway. Gene, 2021, 766, 145163.
[http://dx.doi.org/10.1016/j.gene.2020.145163] [PMID: 32980450]
[23]
Taciak, B.; Pruszynska, I.; Kiraga, L.; Bialasek, M.; Krol, M. Wnt signaling pathway in development and cancer. J. Physiol. Pharmacol., 2018, 69(2), 185-196.
[http://dx.doi.org/10.26402/jpp.2018.2.07] [PMID: 29980141]
[24]
Shang, S.; Hua, F.; Hu, Z.W. The regulation of β-catenin activity and function in cancer: Therapeutic opportunities. Oncotarget, 2017, 8(20), 33972-33989.
[http://dx.doi.org/10.18632/oncotarget.15687] [PMID: 28430641]
[25]
Tian, S.; Peng, P.; Li, J.; Deng, H.; Zhan, N.; Zeng, Z.; Dong, W. SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging, 2020, 12(4), 3574-3593.
[http://dx.doi.org/10.18632/aging.102831] [PMID: 32091407]
[26]
Wang, J.; Cai, H.; Liu, Q.; Xia, Y.; Xing, L.; Zuo, Q.; Zhang, Y.; Chen, C.; Xu, K.; Yin, P.; Chen, T. Cinobufacini inhibits colon cancer invasion and metastasis via suppressing Wnt/β-catenin signaling pathway and EMT. Am. J. Chin. Med., 2020, 48(3), 703-718.
[http://dx.doi.org/10.1142/S0192415X20500354] [PMID: 32329642]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy