The EGFR-HSF1 Axis Accelerates the Tumorigenesis of Pancreatic Cancer

Investigators clarified the mechanisms on early activation of heat shock factor 1 (HSF1) and its role in the pancreatic cancer tumorigenesis.
[Journal of Experimental & Clinical Cancer Research]
Qian, W., Chen, K., Qin, T., Xiao, Y., Li, J., Yue, Y., Zhou, C., Ma, J., Duan, W., Lei, J., Han, L., Li, L., Shen, X., Wu, Z., Ma, Q., & Wang, Z. (2021). The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 25. https://doi.org/10.1186/s13046-020-01823-4 Cite
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Concerted Cell and In Vivo Screen for Pancreatic Ductal Adenocarcinoma (PDA) Chemotherapeutics

Cultured primary PDA cells expressed Rgs16::GFP in response to cytotoxic drugs. A histone deacetylase inhibitor, TSA, stimulated Rgs16::GFP expression in PDA primary cells, potentiated gemcitabine and JQ1 cytotoxicity in cell culture, and Gem + TSA + JQ1 inhibited tumor initiation and progression in vivo.
[Scientific Reports]
Layeghi-Ghalehsoukhteh, S., Pal Choudhuri, S., Ocal, O., Zolghadri, Y., Pashkov, V., Niederstrasser, H., Posner, B. A., Kantheti, H. S., Azevedo-Pouly, A. C., Huang, H., Girard, L., MacDonald, R. J., Brekken, R. A., & Wilkie, T. M. (2020). Concerted cell and in vivo screen for pancreatic ductal adenocarcinoma (PDA) chemotherapeutics. Scientific Reports, 10(1), 20662. https://doi.org/10.1038/s41598-020-77373-8 Cite
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EMC6 Regulates Acinar Apoptosis via APAF1 in Acute and Chronic Pancreatitis

Potential regulatory proteins in pancreatitis were identified by proteomic screen using pancreatic tissues of PRSS1Tg AP mice. Adenoviral shRNA-mediated knockdown of identified proteins, followed by functional assays was performed to validate their roles.
[Cell Death & Disease]
Tan, J., Cao, R., Zhou, L., Zhou, Z., Chen, H., Xu, J., Chen, X., Jin, Y., Lin, J., Qi, Z., Zeng, J., Li, S., Luo, M., Hu, G., Jin, J., & Zhang, G. (2020). EMC6 regulates acinar apoptosis via APAF1 in acute and chronic pancreatitis. Cell Death & Disease, 11(11), 1–13. https://doi.org/10.1038/s41419-020-03177-3 Cite
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Pancreas-Specific Deletion of Protein Kinase D Attenuates Inflammation, Necrosis, and Severity of Acute Pancreatitis

Investigators generated a mouse model with pancreas-specific deletion of PKD3, the predominant PKD isoform in mouse pancreatic acinar cells, by crossing Pkd3flox/flox mice with Pdx1-Cre transgenic mice which express Cre recombinase under the control of the mouse Pdx1 promoter.
[Biochimica Et Biophysica Acta-Molecular Basis of Disease]
Yuan, J., Chheda, C., Piplani, H., Geng, M., Tan, G., Thakur, R., & Pandol, S. J. (2020). Pancreas-specific deletion of protein kinase D attenuates inflammation, necrosis, and severity of acute pancreatitis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 165987. https://doi.org/10.1016/j.bbadis.2020.165987 Cite
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Single-Cell Transcriptomes of Pancreatic Preinvasive Lesions and Cancer Reveal Acinar Metaplastic Cells’ Heterogeneity

Using a reporter gene, scientists identified metaplastic cells that originated from acinar cells and expressed two transcription factors, Onecut2 and Foxq1. Further analyses of metaplastic acinar cell heterogeneity defined six acinar metaplastic cell types and states, including stomach-specific cell types.
[Nature Communications]
Schlesinger, Y., Yosefov-Levi, O., Kolodkin-Gal, D., Granit, R. Z., Peters, L., Kalifa, R., Xia, L., Nasereddin, A., Shiff, I., Amran, O., Nevo, Y., Elgavish, S., Atlan, K., Zamir, G., & Parnas, O. (2020). Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells’ heterogeneity. Nature Communications, 11(1), 4516. https://doi.org/10.1038/s41467-020-18207-z Cite
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The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice

Compromised gustatory sensing, achieved by Gnat3 ablation, enhanced the CXCL1/2 – CXCR2 axis to alter the myeloid-derived suppressor cell population and promoted the progression of metastatic pancreatic ductal adenocarcinoma.
[Cellular and Molecular Gastroenterology and Hepatology]
Hoffman, M. T., Kemp, S. B., Salas-Escabillas, D. J., Zhang, Y., Steele, N. G., The, S., Long, D., Benitz, S., Yan, W., Margolskee, R. F., Bednar, F., Pasca di Magliano, M., Wen, H.-J., & Crawford, H. C. (2020). The Gustatory Sensory G-Protein GNAT3 Suppresses Pancreatic Cancer Progression in Mice. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2020.08.011 Cite
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Lumenal Galectin-9-Lamp2 Interaction Regulates Lysosome and Autophagy to Prevent Pathogenesis in the Intestine and Pancreas

Investigators showed in gut epithelial cells, that galectin-9 was enriched in lysosomes and predominantly bound to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner.
[Nature Communications]
Sudhakar, J. N., Lu, H.-H., Chiang, H.-Y., Suen, C.-S., Hwang, M.-J., Wu, S.-Y., Shen, C.-N., Chang, Y.-M., Li, F.-A., Liu, F.-T., & Shui, J.-W. (2020). Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas. Nature Communications, 11(1), 4286. https://doi.org/10.1038/s41467-020-18102-7 Cite
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Zonation of Pancreatic Acinar Cells in Diabetic Mice

The authors combined single-molecule transcript imaging in the intact pancreas and transcriptomics to identify spatial heterogeneity of acinar cell gene expression. They found that peri-islet acinar cells exhibited a distinct molecular signature in db/db diabetic mice that included upregulation of trypsin family genes and elevated mTOR activity.
[Cell Reports]
Egozi, A., Halpern, K. B., Farack, L., Rotem, H., & Itzkovitz, S. (2020). Zonation of Pancreatic Acinar Cells in Diabetic Mice. Cell Reports, 32(7). https://doi.org/10.1016/j.celrep.2020.108043 Cite
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Extracellular Cold-Inducible RNA-Binding Protein Regulates Neutrophil Extracellular Trap Formation and Tissue Damage in Acute Pancreatitis

Scientists studied the role of extracellular cold-inducible RNA-binding protein, a novel damage-associated-molecular-pattern molecule, in severe acute pancreatitis.
[Laboratory Investigation]
Linders, J., Madhi, R., Rahman, M., Mörgelin, M., Regner, S., Brenner, M., Wang, P., & Thorlacius, H. (2020). Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis. Laboratory Investigation, 1–13. https://doi.org/10.1038/s41374-020-0469-5 Cite
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ANGPTL 4 Exacerbates Pancreatitis by Augmenting Acinar Cell Injury through Upregulation of C5a

The authors’ microarray analysis of pancreatic tissues from mild and severe acute pancreatitis mice models identified angiopoietin‐like 4 (ANGPTL 4) as one of the most significantly upregulated genes.
[EMBO Molecular Medicine]
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BAP1 Is a Haploinsufficient Tumor Suppressor Linking Chronic Pancreatitis to Pancreatic Cancer in Mice

Researchers found that heterozygous loss of histone H2A lysine 119 deubiquitinase BRCA1 Associated Protein-1 associates with a history of chronic pancreatitis and occurs in 25% of pancreatic ductal adenocarcinomas and 40% of acinar cell carcinomas.
[Nature Communications]
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