Abstract PO-117: The role of Hippo signaling in stromal-epithelial interactions in acinar-to-ductal metaplasia and pancreatic cancer initiation

Abstract Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through an interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

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The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

Cancers ◽

10.3390/cancers7030845 ◽

2015 ◽

Vol 7 (3) ◽

pp. 1447-1471 ◽

Cited By ~ 21

Author(s):

Courtney Schaal ◽

Jaya Padmanabhan ◽

Srikumar Chellappan

Keyword(s):

Pancreatic Cancer ◽

Calcium Signaling ◽

Cancer Initiation

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Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer

10.21203/rs.3.rs-104564/v2 ◽

2021 ◽

Author(s):

Wenjie Su ◽

Shikai Zhu ◽

Kai Chen ◽

Hongji Yang ◽

Mingwu Tian ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Critical Role ◽

Biological Role ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Pancreatic Cancer Cells ◽

Independent Functions

Abstract Background: WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer.Methods: The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions.Results: Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells.Conclusions: We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

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Overexpressed WDR3 induces the activation of Hippo pathway by interacting with GATA4 in pancreatic cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01879-w ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Wenjie Su ◽

Shikai Zhu ◽

Kai Chen ◽

Hongji Yang ◽

Mingwu Tian ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Critical Role ◽

Biological Role ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Pancreatic Cancer Cells ◽

Independent Functions

Abstract Background WD repeat domain 3 (WDR3) is involved in a variety of cellular processes including gene regulation, cell cycle progression, signal transduction and apoptosis. However, the biological role of WDR3 in pancreatic cancer and the associated mechanism remains unclear. We seek to explore the immune-independent functions and relevant mechanism for WDR3 in pancreatic cancer. Methods The GEPIA web tool was searched, and IHC assays were conducted to determine the mRNA and protein expression levels of WDR3 in pancreatic cancer patients. MTS, colony formation, and transwell assays were conducted to determine the biological role of WDR3 in human cancer. Western blot analysis, RT-qPCR, and immunohistochemistry were used to detect the expression of specific genes. An immunoprecipitation assay was used to explore protein-protein interactions. Results Our study proved that overexpressed WDR3 was correlated with poor survival in pancreatic cancer and that WDR3 silencing significantly inhibited the proliferation, invasion, and tumor growth of pancreatic cancer. Furthermore, WDR3 activated the Hippo signaling pathway by inducing yes association protein 1 (YAP1) expression, and the combination of WDR3 silencing and administration of the YAP1 inhibitor TED-347 had a synergistic inhibitory effect on the progression of pancreatic cancer. Finally, the upregulation of YAP1 expression induced by WDR3 was dependent on an interaction with GATA binding protein 4 (GATA4), the transcription factor of YAP1, which interaction induced the nuclear translocation of GATA4 in pancreatic cancer cells. Conclusions We identified a novel mechanism by which WDR3 plays a critical role in promoting pancreatic cancer progression by activating the Hippo signaling pathway through the interaction with GATA4. Therefore, WDR3 is potentially a therapeutic target for pancreatic cancer treatment.

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Targeting Fibrosis: The Bridge That Connects Pancreatitis and Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22094970 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4970

Author(s):

Can Huang ◽

Juan Iovanna ◽

Patricia Santofimia-Castaño

Keyword(s):

Pancreatic Cancer ◽

Stress Proteins ◽

Nuclear Protein ◽

Pancreatic Tissue ◽

Cellular Stress Response ◽

Pancreatic Fibrosis ◽

Pathological Feature ◽

Cancer Initiation ◽

Key Driver

Pancreatic fibrosis is caused by the excessive deposits of extracellular matrix (ECM) and collagen fibers during repeated necrosis to repair damaged pancreatic tissue. Pancreatic fibrosis is frequently present in chronic pancreatitis (CP) and pancreatic cancer (PC). Clinically, pancreatic fibrosis is a pathological feature of pancreatitis and pancreatic cancer. However, many new studies have found that pancreatic fibrosis is involved in the transformation from pancreatitis to pancreatic cancer. Thus, the role of fibrosis in the crosstalk between pancreatitis and pancreatic cancer is critical and still elusive; therefore, it deserves more attention. Here, we review the development of pancreatic fibrosis in inflammation and cancer, and we discuss the therapeutic strategies for alleviating pancreatic fibrosis. We further propose that cellular stress response might be a key driver that links fibrosis to cancer initiation and progression. Therefore, targeting stress proteins, such as nuclear protein 1 (NUPR1), could be an interesting strategy for pancreatic fibrosis and PC treatment.

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PET/CT IN THE DIAGNOSIS OF PANCREATIC CANCER: LITERATURE REVIEW

Medical Visualization ◽

10.24835/1607-0763-2018-1-57-67 ◽

2018 ◽

pp. 57-67

Author(s):

P. E. Tulin ◽

M. B. Dolgushin ◽

D. I. Nevzorov ◽

P. V. Kochergin ◽

Yu. I. Patyutko

Keyword(s):

Pancreatic Cancer ◽

Literature Review ◽

Pancreatic Neoplasms ◽

Poor Prognosis ◽

Modern Imaging ◽

Pet Ct

Pancreatic cancer has a poor prognosis, often because most pancreatic neoplasms are found to be unresectable at diagnosis. Early staging of the tumor process can change the tactics of treatment and affect the survival of patients. The purpose of this review is to provide an overview of pancreatic cancer and the role of modern imaging in its diagnosis with an emphasis on PET/CT with a various radiopharmaceuticals.

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