Exploiting Oxidative Phosphorylation to Promote the Stem and Immunoevasive Properties of Pancreatic Cancer Stem Cells

Investigators describe a 2D in vitro system for long-term enrichment of pancreatic cancer stem cells (CSCs) that was amenable to biological and CSC-specific studies.
[Nature Communications]
Valle, S., Alcalá, S., Martin-Hijano, L., Cabezas-Sáinz, P., Navarro, D., Muñoz, E. R., Yuste, L., Tiwary, K., Walter, K., Ruiz-Cañas, L., Alonso-Nocelo, M., Rubiolo, J. A., González-Arnay, E., Heeschen, C., Garcia-Bermejo, L., Hermann, P. C., Sánchez, L., Sancho, P., Fernández-Moreno, M. Á., & Sainz, B. (2020). Exploiting oxidative phosphorylation to promote the stem and immunoevasive properties of pancreatic cancer stem cells. Nature Communications, 11(1), 5265. https://doi.org/10.1038/s41467-020-18954-z Cite
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Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell-of-Origin

Researchers FACS-purified epithelial cells from human pancreatic ductal adenocarcinoma and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes.
[Cancer Discovery]
Espinet, E., Gu, Z., Imbusch, C. D., Giese, N. A., Buscher, M., Safavi, M., Weisenburger, S., Klein, C., Vogel, V., Falcone, M., Insua-Rodriguez, J., Reitberger, M., Thiel, V., Kossi, S. O., Muckenhuber, A., Sarai, K., Lee, A. Y., Backx, E., Zarei, S., … Trumpp, A. (2020). Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell-of-origin. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1202 Cite
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Non-Coding RNA Biomarkers in Pancreatic Ductal Adenocarcinoma

The authors focus on three types of well-established ncRNAs — microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) — and discuss their potential as diagnostic, prognostic and predictive biomarkers in pancreatic ductal adenocarcinoma.
[Seminars in Cancer Biology]
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Active Transportation of Liposome Enhances Tumor Accumulation, Penetration, and Therapeutic Efficacy

When GCSDL contacted with tumor vascular endothelial cells, the overexpressed γ‐glutamyltranspeptidase enzyme on cytomembrane catalyzed the hydrolysis of GSH to generate cationic primary amines.
[Small]
Wang, G., Wu, B., Li, Q., Chen, S., Jin, X., Liu, Y., Zhou, Z., Shen, Y., & Huang, P. (n.d.). Active Transportation of Liposome Enhances Tumor Accumulation, Penetration, and Therapeutic Efficacy. Small, n/a(n/a), 2004172. https://doi.org/10.1002/smll.202004172 Cite
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Suppression of Pancreatic Cancer Liver Metastasis by Secretion-Deficient ITIH5

Investigators expressed mutant ITIH5 with deletion of the N-terminal secretion sequence (ITIH5Δs) in highly metastatic human pancreatic ductal adenocarcinoma (PDAC) cell lines. They used a human tissue microarray to compare ITIH5 levels in uninvolved pancreas, primary and metastatic PDAC.
[British Journal of Cancer]
Young, E. D., Manley, S. J., Beadnell, T. C., Shearin, A. E., Sasaki, K., Zimmerman, R., Kauffman, E., Vivian, C. J., Parasuram, A., Iwakuma, T., Grandgenett, P. M., Hollingsworth, M. A., O’Neil, M., & Welch, D. R. (2020). Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5. British Journal of Cancer, 1–10. https://doi.org/10.1038/s41416-020-01093-z Cite
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Molecular Alterations and Targeted Therapy in Pancreatic Ductal Adenocarcinoma

The authors focus on recent pre-clinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for pancreatic ductal adenocarcinoma.
[Journal of Hematology & Oncology]
Qian, Y., Gong, Y., Fan, Z., Luo, G., Huang, Q., Deng, S., Cheng, H., Jin, K., Ni, Q., Yu, X., & Liu, C. (2020). Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma. Journal of Hematology & Oncology, 13(1), 130. https://doi.org/10.1186/s13045-020-00958-3 Cite
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Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas

Scientists interrogated purified sorted tumor fractions from a series of 15 tumor samples with whole-genome copy-number variant, whole-exome sequencing, and assay for transposase-accessible chromatin using sequencing analyses.
[Cancer Research]
Lenkiewicz, E., Malasi, S., Hogenson, T. L., Flores, L. F., Barham, W., Phillips, W. J., Roesler, A. S., Chambers, K. R., Rajbhandari, N., Hayashi, A., Antal, C. E., Downes, M., Grandgenett, P. M., Hollingsworth, M. A., Cridebring, D., Xiong, Y., Lee, J.-H., Ye, Z., Yan, H., … Barrett, M. T. (2020). Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0078 Cite
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Cholesterol Pathway Inhibition Induces TGF-β Signaling to Promote Basal Differentiation in Pancreatic Cancer

The authors defined a mechanism by which cholesterol metabolism controls the development and differentiation of pancreatic ductal adenocarcinoma.
[Cancer Cell]
Gabitova-Cornell, L., Surumbayeva, A., Peri, S., Franco-Barraza, J., Restifo, D., Weitz, N., Ogier, C., Goldman, A. R., Hartman, T. R., Francescone, R., Tan, Y., Nicolas, E., Shah, N., Handorf, E. A., Cai, K. Q., O’Reilly, A. M., Sloma, I., Chiaverelli, R., Moffitt, R. A., … Astsaturov, I. (2020). Cholesterol Pathway Inhibition Induces TGF-β Signaling to Promote Basal Differentiation in Pancreatic Cancer. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2020.08.015 Cite
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Circadian Dysregulation of the TGFβ/SMAD4 Pathway Modulates Metastatic Properties and Cell Fate Decisions in Pancreatic Cancer Cells

Scientists used an in vitro pancreatic ductal adenocarcinoma model of SMAD4 positive and negative cells to investigate the interplay between circadian rhythms, the TGFβ canonical signaling pathway and its impact on tumor malignancy.
[iScience]
Li, Y., Basti, A., Yalçin, M., & Relógio, A. (2020). Circadian dysregulation of the TGFβ/SMAD4 pathway modulates metastatic properties and cell fate decisions in pancreatic cancer cells. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101551 Cite
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The Actin Modulator hMENA Regulates GAS6-AXL Axis and Pro-Tumor Cancer/Stromal Cell Cooperation

LC‐MS/MS proteomic analysis revealed that cancer‐associated fibroblasts (CAFs) that overexpressed hMENAΔv6 secreted the AXL ligand GAS6, favoring the invasiveness of AXL‐expressing pancreatic ductal adenocarcinoma and non‐small cell lung cancer cells.
[EMBO Reports]
Melchionna, R., Spada, S., Di Modugno, F., D’Andrea, D., Di Carlo, A., Panetta, M., Mileo, A. M., Sperduti, I., Antoniani, B., Gallo, E., Lawlor, R. T., Piemonti, L., Visca, P., Milella, M., Grazi, G. L., Facciolo, F., Chen, E., Scarpa, A., & Nisticò, P. (2020). The actin modulator hMENA regulates GAS6-AXL axis and pro-tumor cancer/stromal cell cooperation. EMBO Reports, n/a(n/a), e50078. https://doi.org/10.15252/embr.202050078 Cite
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EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6

Scientists characterized the mechanistic and functional implications of the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2) in controlling pancreatic ductal adenocarcinoma plasticity, dedifferentiation, and molecular subtype identity.
[Cancer Research]
Patil, S., Steuber, B., Kopp, W., Kari, V., Urbach, L., Wang, X., Küffer, S., Bohnenberger, H., Spyropoulou, D., Zhang, Z., Versemann, L., Bösherz, M. S., Brunner, M., Gaedcke, J., Ströbel, P., Zhang, J.-S., Neesse, A., Ellenrieder, V., Singh, S. K., … Hessmann, E. (2020). EZH2 regulates pancreatic cancer subtype identity and tumor progression via transcriptional repression of GATA6. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0672 Cite
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