Skip to main content
Erschienen in: Digestive Diseases and Sciences 2/2021

31.03.2020 | Original Article

PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma

verfasst von: Xin He, Fan Meng, Zhong-jian Yu, Xiong-jie Zhu, Ling-yu Qin, Xiao-ran Wu, Zhi-le Liu, Ying Li, Yan-fang Zheng

Erschienen in: Digestive Diseases and Sciences | Ausgabe 2/2021

Einloggen, um Zugang zu erhalten

Abstract

Background

Phospholipase C delta 1 (PLCD1) has been found to be abnormally expressed in various cancers. However, the potential roles of PLCD1 in esophageal squamous cell carcinoma (ESCC) are still unknown.

Methods

Western blot and qPCR were used to explore PLCD1 expression in various ESCC cells. MTT, colony formation assays, wound-healing assay, and transwell cell invasion assay were used to examine the cell viability in vitro. Western blot, qPCR, and luciferase assays were used to investigate the effects of PLCD1 on Wnt/β-catenin signaling pathway. The xenograft models in nude mice were established to explore the roles of PLCD1 in vivo.

Results

We found that the expression of PLCD1 in ESCC cells was significantly downregulated than that in normal esophageal epithelial cells. In addition, upregulation of PLCD1 decreased the capacity of TE-1 and EC18 cells in proliferation, invasion, and migration. Then, the expression of β-catenin/p-β-catenin, C-myc, cyclin D1, MMP9, and MMP7 was investigated. PLCD1 activity was found to be negatively associated with the expression of β-catenin, C-myc, cyclin D1, MMP9, and MMP7. Finally, the activity of PLCD1 in inhibiting ESCC proliferation in vivo was validated.

Conclusion

The inhibitory effects of PLCD1 on the proliferation, invasion, and migration of TE-1 and EC18 cells might be associated with inhibition of Wnt/β-catenin signaling pathway. PLCD1 played a key role in inhibiting ESCC carcinogenesis and progression in patients with ESCC.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Bollschweiler E, Plum P, Mönig SP, et al. Current and future treatment options for esophageal cancer in the elderly. Expert Opin Pharmacother. 2017;18:1001–1010.CrossRef Bollschweiler E, Plum P, Mönig SP, et al. Current and future treatment options for esophageal cancer in the elderly. Expert Opin Pharmacother. 2017;18:1001–1010.CrossRef
3.
Zurück zum Zitat Rustgi AK, El-Serag HBJNEJM. Esophageal carcinoma. N Engl J Med. 2014;371:2499–2509.CrossRef Rustgi AK, El-Serag HBJNEJM. Esophageal carcinoma. N Engl J Med. 2014;371:2499–2509.CrossRef
4.
Zurück zum Zitat Tran GD, Sun XD, Abnet CC, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 2005;113:456–463.CrossRef Tran GD, Sun XD, Abnet CC, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer. 2005;113:456–463.CrossRef
5.
Zurück zum Zitat Lattanzio R, Piantelli M, Falasca M. Role of phospholipase C in cell invasion and metastasis. Adv Biol Regul. 2013;53:309–318.CrossRef Lattanzio R, Piantelli M, Falasca M. Role of phospholipase C in cell invasion and metastasis. Adv Biol Regul. 2013;53:309–318.CrossRef
6.
Zurück zum Zitat Fukami K. Structure, regulation, and function of phospholipase C isozymes. J Biochem. 2002;131:293–299.CrossRef Fukami K. Structure, regulation, and function of phospholipase C isozymes. J Biochem. 2002;131:293–299.CrossRef
7.
Zurück zum Zitat Qing S, Xinrong L, Dejuan Y, et al. Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β-catenin/MMP7 signalling. Oncotarget. 2017;8:29056–29066.CrossRef Qing S, Xinrong L, Dejuan Y, et al. Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β-catenin/MMP7 signalling. Oncotarget. 2017;8:29056–29066.CrossRef
8.
Zurück zum Zitat Mu H, Wang N, Zhao L, et al. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer. Exp Cell Res. 2015;332:179–189.CrossRef Mu H, Wang N, Zhao L, et al. Methylation of PLCD1 and adenovirus-mediated PLCD1 overexpression elicits a gene therapy effect on human breast cancer. Exp Cell Res. 2015;332:179–189.CrossRef
9.
Zurück zum Zitat Hu XT, Zhang FB, Fan YC, et al. Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer. Oncogene. 2009;28:2466–2475.CrossRef Hu XT, Zhang FB, Fan YC, et al. Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer. Oncogene. 2009;28:2466–2475.CrossRef
10.
Zurück zum Zitat Zhu X, Wang J, Li L, et al. GPX3 suppresses tumor migration and invasion via the FAK/AKT pathway in esophageal squamous cell carcinoma. Am J Transl Res. 2018;10:1908–1920.PubMedPubMedCentral Zhu X, Wang J, Li L, et al. GPX3 suppresses tumor migration and invasion via the FAK/AKT pathway in esophageal squamous cell carcinoma. Am J Transl Res. 2018;10:1908–1920.PubMedPubMedCentral
11.
Zurück zum Zitat Bian ZQ, Luo Y, Guo F, et al. Overexpressed ACP5 has prognostic value in colorectal cancer and promotes cell proliferation andtumorigenesis via FAK/PI3K/AKT signaling pathway. Am J Cancer Res. 2019;9:22–35.PubMedPubMedCentral Bian ZQ, Luo Y, Guo F, et al. Overexpressed ACP5 has prognostic value in colorectal cancer and promotes cell proliferation andtumorigenesis via FAK/PI3K/AKT signaling pathway. Am J Cancer Res. 2019;9:22–35.PubMedPubMedCentral
12.
Zurück zum Zitat Shang S, Hua F, Hu ZW. The regulation of beta-catenin activity and function in cancer: therapeutic opportunities. Oncotarget. 2017;8:33972–33989.CrossRef Shang S, Hua F, Hu ZW. The regulation of beta-catenin activity and function in cancer: therapeutic opportunities. Oncotarget. 2017;8:33972–33989.CrossRef
13.
Zurück zum Zitat Lin DC, Wang MR, Koeffler HP. Genomic and epigenomic aberrations in esophageal squamous cell carcinoma and implications for patients. Gastroenterology. 2018;154:374–389.CrossRef Lin DC, Wang MR, Koeffler HP. Genomic and epigenomic aberrations in esophageal squamous cell carcinoma and implications for patients. Gastroenterology. 2018;154:374–389.CrossRef
14.
Zurück zum Zitat Xiang T, Li L, Fan Y, et al. PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer. Cancer Biol Ther. 2010;10:520–527.CrossRef Xiang T, Li L, Fan Y, et al. PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer. Cancer Biol Ther. 2010;10:520–527.CrossRef
15.
Zurück zum Zitat Danielsen SA, Cekaite L, Agesen TH, et al. Phospholipase C isozymes are deregulated in colorectal cancer–insights gained from gene set enrichment analysis of the transcriptome. PLoS ONE. 2011;6:e24419.CrossRef Danielsen SA, Cekaite L, Agesen TH, et al. Phospholipase C isozymes are deregulated in colorectal cancer–insights gained from gene set enrichment analysis of the transcriptome. PLoS ONE. 2011;6:e24419.CrossRef
16.
Zurück zum Zitat Huang SP, Liu PY, Kuo CJ, et al. The Gαh-PLCδ1 signaling axis drives metastatic progression in triple-negative breast cancer. J Hematol Oncol. 2017;10:114.CrossRef Huang SP, Liu PY, Kuo CJ, et al. The Gαh-PLCδ1 signaling axis drives metastatic progression in triple-negative breast cancer. J Hematol Oncol. 2017;10:114.CrossRef
17.
Zurück zum Zitat Song JJ, Liu Q, Li Y, et al. Epigenetic inactivation of PLCD1 in chronic myeloid leukemia. Int J Mol Med. 2012;30:179–184.PubMed Song JJ, Liu Q, Li Y, et al. Epigenetic inactivation of PLCD1 in chronic myeloid leukemia. Int J Mol Med. 2012;30:179–184.PubMed
18.
Zurück zum Zitat Dakeng S, Duangmano S, Jiratchariyakul W, et al. Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus. J Cell Biochem. 2012;113:49–60.CrossRef Dakeng S, Duangmano S, Jiratchariyakul W, et al. Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus. J Cell Biochem. 2012;113:49–60.CrossRef
19.
Zurück zum Zitat Chen C, Zhao M, Tian A, et al. Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells. Oncotarget. 2015;6:17570–17583.CrossRef Chen C, Zhao M, Tian A, et al. Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells. Oncotarget. 2015;6:17570–17583.CrossRef
20.
Zurück zum Zitat MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17:9–26.CrossRef MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17:9–26.CrossRef
21.
Zurück zum Zitat Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J. 2012;31:2714–2736.CrossRef Valenta T, Hausmann G, Basler K. The many faces and functions of β-catenin. EMBO J. 2012;31:2714–2736.CrossRef
22.
Zurück zum Zitat Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322.CrossRef Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322.CrossRef
23.
Zurück zum Zitat Rennoll S, Yochum G. Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer. World J Biol Chem. 2015;6:290–300.CrossRef Rennoll S, Yochum G. Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer. World J Biol Chem. 2015;6:290–300.CrossRef
24.
Zurück zum Zitat Weber JD, Raben DM, Phillips PJ, et al. Sustained activation of erace-ularsignal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase. Biochem J. 1997;326:61–68.CrossRef Weber JD, Raben DM, Phillips PJ, et al. Sustained activation of erace-ularsignal-regulated kinase 1 (ERK1) is required for the continued expression of cyclin D1 in G1 phase. Biochem J. 1997;326:61–68.CrossRef
25.
Zurück zum Zitat Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med (Berl). 2016;94:1313–1326.CrossRef Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med (Berl). 2016;94:1313–1326.CrossRef
Metadaten
Titel
PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma
verfasst von
Xin He
Fan Meng
Zhong-jian Yu
Xiong-jie Zhu
Ling-yu Qin
Xiao-ran Wu
Zhi-le Liu
Ying Li
Yan-fang Zheng
Publikationsdatum
31.03.2020
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 2/2021
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-020-06218-1

Weitere Artikel der Ausgabe 2/2021

Digestive Diseases and Sciences 2/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.