scholarly journals The clinical relevance of the Hippo pathway in pancreatic ductal adenocarcinoma

2020 ◽  
Author(s):  
Richard Drexler ◽  
Mirco Küchler ◽  
Kim C. Wagner ◽  
Tim Reese ◽  
Bernd Feyerabend ◽  
...  
Keyword(s):  
Cancer Research ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Clinical Relevance ◽  
Hippo Pathway ◽  
Ductal Adenocarcinoma ◽  
Proliferative Potential ◽  
The Past ◽  
Pancreatic Tumour ◽  
The Hippo Pathway ◽  
Disease Free

Abstract Purpose The Hippo pathway has broadened in cancer research in the past decade and revealed itself to be an important driver for tumorigenesis and metastatic spread. In this study, we investigated the clinical relevance of the Hippo pathway with regard to metastatic invasion, patients’ outcome and histopathological features. Methods Protein expression of components of the Hippo pathway were analyzed by immunohistochemistry (IHC) using paraffin-embedded tissue from 103 patients who had been diagnosed with pancreatic ductal adenocarcinoma and had undergone surgery. Results were correlated with clinicopathological data, disease-free and overall survival. Results Immunohistochemistry studies in pancreatic tumour tissues revealed a significant upregulation of MST1, MST2, pLATS, pYAP and 14-3-3, representing the active Hippo pathway, in non-metastasized patients (p < 0.01). In turn, the pathway is more inactive in metastasized patients and relating liver metastases as LATS1, LATS2, YAP, transcriptional factors TEAD2 and TEAD3 were upregulated in these patients (p < 0.01). A higher pYAP expression was associated with a favorable OS and DFS. Conclusion The Hippo pathway is inactive in metastasized patients releasing the pro-metastatic and proliferative potential of the pathway. Furthermore, our study underlines the prognostic relevance of the Hippo pathway as a shift in the balance towards the inactive pathway predicts an unfavorable OS and DFS.

HSP27 regulates the Hippo pathway and thereby promotes metastasis in pancreatic ductal adenocarcinoma

Pancreatology ◽  
2019 ◽  
Vol 19 ◽  
pp. S160
Author(s):  
Richard Drexler ◽  
Kim C. Wagner ◽  
Mirco Küchler ◽  
Karl-Jürgen Oldhafer
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Hippo Pathway ◽  
Ductal Adenocarcinoma ◽  
The Hippo Pathway

scholarly journals Hypoxia induces oncogene yes-associated protein 1 nuclear translocation to promote pancreatic ductal adenocarcinoma invasion via epithelial–mesenchymal transition

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769168 ◽  
Author(s):  
Honglong Wei ◽  
Zongzhen Xu ◽  
Feng Liu ◽  
Fuhai Wang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Hippo Pathway ◽  
Hypoxia Inducible Factor ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition ◽  
Hypoxia Inducible Factor 1Α ◽  
Tumor Microenvironments ◽  
Adenocarcinoma Cells ◽  
The Hippo Pathway

Pancreatic ductal adenocarcinoma is one of the most lethal cancers. The Hippo pathway is involved in tumorigenesis and remodeling of tumor microenvironments. Hypoxia exists in the microenvironment of solid tumors, including pancreatic ductal adenocarcinoma and plays a vital role in tumor progression and metastasis. However, it remains unclear how hypoxia interacts with the Hippo pathway to regulate these events. In this study, expressions of yes-associated protein 1 and hypoxia-inducible factor-1α were found to be elevated in pancreatic ductal adenocarcinoma samples compared with those in matched adjacent non-tumor samples. Moreover, hypoxia-inducible factor-1α expression was positively correlated with yes-associated protein 1 level in pancreatic ductal adenocarcinoma tissues. The higher expression of nuclear yes-associated protein 1 was associated with poor histological grade and prognosis for pancreatic ductal adenocarcinoma patients. In vitro, yes-associated protein 1 was highly expressed in pancreatic ductal adenocarcinoma cells. Depletion of yes-associated protein 1 inhibited the invasion of pancreatic ductal adenocarcinoma cells via downregulation of Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-13, and upregulation of E-cadherin. In addition, hypoxia promoted the invasion of pancreatic ductal adenocarcinoma cells via regulating the targeted genes. Hypoxia also deactivated the Hippo pathway and induced yes-associated protein 1 nuclear translocation. Furthermore, depletion of yes-associated protein 1 or hypoxia-inducible factor-1α suppressed the invasion of pancreatic ductal adenocarcinoma cells under hypoxia. Mechanism studies showed that nuclear yes-associated protein 1 interacted with hypoxia-inducible factor-1α and activated Snail transcription to participate in epithelial–mesenchymal transition–mediated and matrix metalloproteinase–mediated remodeling of tumor microenvironments. Collectively, yes-associated protein 1 is an independent prognostic predictor that interacts with hypoxia-inducible factor-1α to enhance the invasion of pancreatic cancer cells and remodeling of tumor microenvironments. Therefore, yes-associated protein 1 may serve as a novel promising target to enhance therapeutic effects for treating pancreatic cancer.

scholarly journals The tumor suppressor BAP1 regulates the Hippo pathway in pancreatic ductal adenocarcinoma

2020 ◽  
pp. canres.1704.2019 ◽  
Author(s):  
Ho-June Lee ◽  
Trang Pham ◽  
Matthew T Chang ◽  
Dwight Barnes ◽  
Allen G Cai ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Hippo Pathway ◽  
Ductal Adenocarcinoma ◽  
The Hippo Pathway

Precursors of pancreatic cancer in background of chronic opisthorchiasis

2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Morphological Data ◽  
Small Samples ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Opisthorchis Felineus ◽  
Disease Free

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.

scholarly journals Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Beate Gündel ◽  
Xinyuan Liu ◽  
Matthias Löhr ◽  
Rainer Heuchel
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ex Vivo ◽  
Treatment Options ◽  
3D Cell Culture ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
The Past ◽  
Slow Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

scholarly journals Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2750
Author(s):  
Pierre-Olivier Frappart ◽  
Thomas G. Hofmann
Keyword(s):  
Personalized Medicine ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Response ◽  
Treatment Options ◽  
Response Prediction ◽  
Ductal Adenocarcinoma ◽  
Chemotherapy Treatment ◽  
The Past ◽  
Therapeutic Tools ◽  
And Personalized Medicine

Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.

Abstract A9: The pancreatic ductal adenocarcinoma project at the Ontario Institute for Cancer Research.

2012 ◽  
Author(s):  
Kimberly N. Begley ◽  
Debabrata Mukhopadhyay ◽  
Gloria M. Petersen ◽  
Alexei Protopopov ◽  
Sarah Thayer ◽  
...  
Keyword(s):  
Cancer Research ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Ductal Adenocarcinoma
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