Identification of Genes Associated with Liver Metastasis in Pancreatic Cancer Reveals PCSK6 as a Crucial Mediator
He H, Zhang S, Yang H, Xu P, Kutschick I, Pfeffer S, Britzen-Laurent N, Grützmann R, Fu D, Pilarsky C (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 15
Article Number: 241
Journal Issue: 1
Abstract
Liver metastasis occurs frequently in patients with pancreatic cancer. We analyzed the molecular profiling in liver metastatic lesions aiming to uncover novel genes responsible for tumor progression. Bioinformatics analysis was applied to identify genes directing liver metastasis. CRISPR/Cas9 technology was used to knock out the candidate gene. Proliferation assays, colony formation assays, cell cycle analysis, migration assays, wound healing assays, Immunofluorescence analysis, and the tumor xenograft model of intrasplenic injection were adopted to evaluate the effects of PCSK6 inactivation on cell growth, migration and liver metastasis. GSEA and Western blot were used to investigate the corresponding signaling pathway. PCSK6 was one of the obtained liver-metastasis-related genes in pancreatic cancer. PCSK6 inactivation inhibited cell growth and cell migration, due to G0/G1 cell cycle arrest and the remodeling of cell–cell junctions or the cell skeleton, respectively. PCSK6 inactivation led to fewer counts and lower outgrowth rates of liver metastatic niches in vivo. The Raf-MEK1/2-ERK1/2 axis was repressed by PCSK6 inactivation. Accordingly, we found PCSK6 inactivation could inhibit cell growth, cell migration, and liver metastasis, and explored the role of the Raf-MEK1/2-ERK1/2 axis in PCSK6 inactivation. PCSK6-targeted therapy might represent a novel approach for combatting liver metastasis in pancreatic cancer.
Authors with CRIS profile
Shuman Zhang
Professur für Chirurgische Forschung
Hai Yang
Department of Surgery
Pengyan Xu
Professur für Chirurgische Forschung
Sina Pfeffer
Medizinische Fakultät
Nathalie Britzen-Laurent
Medizinische Fakultät
Robert Grützmann
Department of Surgery
Christian Pilarsky
Professur für Chirurgische Forschung
Involved external institutions
China (CN)How to cite
APA:
He, H., Zhang, S., Yang, H., Xu, P., Kutschick, I., Pfeffer, S.,... Pilarsky, C. (2023). Identification of Genes Associated with Liver Metastasis in Pancreatic Cancer Reveals PCSK6 as a Crucial Mediator. Cancers, 15(1). https://dx.doi.org/10.3390/cancers15010241
MLA:
He, Hang, et al. "Identification of Genes Associated with Liver Metastasis in Pancreatic Cancer Reveals PCSK6 as a Crucial Mediator." Cancers 15.1 (2023).
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