Products Cited in Publications Worldwide Twist1 Regulates the Immune Checkpoint VISTA and Promotes the Proliferation, Migration and Progression of Pancreatic Cancer Cells

Twist1 Regulates the Immune Checkpoint VISTA and Promotes the Proliferation, Migration and Progression of Pancreatic Cancer Cells

Topcu, Kubra Sena Bas; Cacan, Ercan

DOI: PMID:

Abstract

Pancreatic cancer is one of the deadliest malignant tumours worldwide. Despite the developments in the treatments of pancreatic cancer, survival rates remain at a low level, and the mechanisms underlying the aggressive course of the cancer are not fully understood. VISTA is an immune checkpoint and has recently become a significant target in cancer treatment; however, the roles of VISTA in the development of pancreatic cancer have largely remained unknown. Histone deacetylase inhibitors (HDACi) have been reported to reverse the epithelial-mesenchymal transition (EMT) and may enhance the efficacy of anti-PD-1 therapy. The PD-L1/PD-1 immune checkpoint targeted by this therapy shares structural similarity with VISTA. Moreover, combination therapy of vorinostat and anti-PD-1 has been shown to significantly reduce tumour growth by suppressing the transcription factor c-Myc. Therefore, in this study, we aim to investigate the genes that are associated with EMT and explore the potential mechanism involving Twist1, a proto-oncogene, and VISTA in pancreatic cancer. We also sought to determine the synergistic effects of an HDACi, vorinostat, in combination with Twist1-siRNA on VISTA expression in pancreatic cancer cells’ viability and proliferation. Our results revealed that Twist1 blockade in combination with vorinostat in pancreatic cancer cells suppresses EMT-associated genes and the immune checkpoint VISTA compared to treatments administered alone. As a result, identifying the genes associated with EMT in pancreatic cancer and understanding the role of Twist1 in this process is a crucial step to contribute to the identification of new targets for pancreatic cancer treatment and the improvement of existing treatment strategies.

Keywords

EMT ; immune checkpoint ; pancreatic cancer ; Twist1 ; vorinostat

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Vorinostat

A234507149647-78-998%

Vorinostat

14.0/100mg

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