H2A.Z Overexpression Suppresses Senescence and Chemosensitivity in Pancreatic Ductal Adenocarcinoma

Scientists demonstrated that the histone variant H2A.Z was highly expressed in PDAC cell lines and PDAC patients and that its overexpression correlated with poor prognosis.
[Oncogene]
Ávila-López, P. A., Guerrero, G., Nuñez-Martínez, H. N., Peralta-Alvarez, C. A., Hernández-Montes, G., Álvarez-Hilario, L. G., Herrera-Goepfert, R., Albores-Saavedra, J., Villegas-Sepúlveda, N., Cedillo-Barrón, L., Montes-Gómez, A. E., Vargas, M., Schnoor, M., Recillas-Targa, F., & Hernández-Rivas, R. (2021). H2A.Z overexpression suppresses senescence and chemosensitivity in pancreatic ductal adenocarcinoma. Oncogene, 1–16. https://doi.org/10.1038/s41388-021-01664-1 Cite
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NAD+ Depletion by Type I Interferon Signaling Sensitizes Pancreatic Cancer Cells to NAMPT Inhibition

The authors showed that interferon signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14.
[Proceedings of the National Academy of Sciences of the United States of America]
Moore, A. M., Zhou, L., Cui, J., Li, L., Wu, N., Yu, A., Poddar, S., Liang, K., Abt, E. R., Kim, S., Ghukasyan, R., Khachatourian, N., Pagano, K., Elliott, I., Dann, A. M., Riahi, R., Le, T., Dawson, D. W., Radu, C. G., & Donahue, T. R. (2021). NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition. Proceedings of the National Academy of Sciences, 118(8). https://doi.org/10.1073/pnas.2012469118 Cite
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RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer

The authors proposed RAD50-interacting protein 1 (RINT1) as an essential mediator of cellular homeostasis in PDAC. RINT1 depletion caused severe growth defects in vitro associated with accumulation of DNA double-strand breaks, G2 cell cycle arrest, disruption of Golgi-ER homeostasis, and cell death.
[Cancer Research]
Arnold, F., Gout, J., Wiese, H., Weissinger, S., Roger, E., Perkhofer, L., Walter, K., Scheible, J., Prelli-Bozzo, C., Lechel, A., Ettrich, T. J., Azoitei, N., Hao, L., Fuerstberger, A., Kaminska, E. K., Sparrer, K. M. J., Rasche, V., Wiese, S., Kestler, H. A., … Kleger, A. (2021). RINT1 regulates SUMOylation and the DNA damage response to preserve cellular homeostasis in pancreatic cancer. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-2633 Cite
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MGST1 Is a Redox-Sensitive Repressor of Ferroptosis in Pancreatic Cancer Cells

Scientists showed a key role of MGST1 in inhibiting ferroptosis in cell cultures and mouse xenograft models. Ferroptosis activators induced MGST1 upregulation in human PDAC cell lines in an NFE2L2-dependent manner.
[Cell Chemical Biology]
Kuang, F., Liu, J., Xie, Y., Tang, D., & Kang, R. (2021). MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells. Cell Chemical Biology, 0(0). https://doi.org/10.1016/j.chembiol.2021.01.006 Cite
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Functional Expression of the Transient Receptor Potential Ankyrin Type 1 Channel in Pancreatic Adenocarcinoma Cells

Investigators report the endogenous expression of transient receptor potential ankyrin type 1 (TRPA1) channels in human pancreatic adenocarcinoma cell lines and provided insights into the function of the TRPA1 protein in the Panc-1 cell line.
[Scientific Reports]
Cojocaru, F., Şelescu, T., Domocoş, D., Măruţescu, L., Chiritoiu, G., Chelaru, N.-R., Dima, S., Mihăilescu, D., Babes, A., & Cucu, D. (2021). Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells. Scientific Reports, 11(1), 2018. https://doi.org/10.1038/s41598-021-81250-3 Cite
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MUC4 Enhances Gemcitabine Resistance and Malignant Behavior in Pancreatic Cancer Cells Expressing Cancer-Associated Short O-Glycans

Scientists genetically knocked out MUC4 in PDAC cells that did not express and did express truncated O-glycans using CRISPR/Cas9 technology.
[Cancer Letters]
Sagar, S., Leiphrakpam, P. D., Thomas, D., McAndrews, K. L., Caffrey, T. C., Swanson, B. J., Clausen, H., Wandall, H. H., Hollingsworth, M. A., & Radhakrishnan, P. (2021). MUC4 enhances gemcitabine resistance and malignant behaviour in pancreatic cancer cells expressing cancer-associated short O-glycans. Cancer Letters. https://doi.org/10.1016/j.canlet.2021.01.015 Cite
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CEACAM7 Is an Effective Target for CAR T-cell Therapy of Pancreatic Ductal Adenocarcinoma

Scientists identified CEACAM7 as a potential therapeutic target in PDAC and described the development of CEACAM7-targeted CAR T cells with efficacy against PDAC.
[Clinical Cancer Research]
Raj, D., Nikolaidi, M., Garces, I., Lorizio, D., Castro, N. M., Caiafa, S. G., Moore, K., Brown, N. F., Kocher, H. M., Duan, X., Nelson, B. H., Lemoine, N. R., & Marshall, J. F. (2021). CEACAM7 Is an Effective Target for CAR T-cell Therapy of Pancreatic Ductal Adenocarcinoma. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-19-2163 Cite
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Visualization of Stem Cell Activity in Pancreatic Cancer Expansion by Direct Lineage Tracing with Live Imaging

Using genetic lineage tracing with a dual-recombinase system and live imaging, scientists showed that Dclk1+ tumor cells continuously provided progeny cells within pancreatic intraepithelial neoplasia, primary and metastatic PDAC and PDAC-derived spheroids in vivo and in vitro.
[eLife]
Maruno, T., Fukuda, A., Goto, N., Tsuda, M., Ikuta, K., Hiramatsu, Y., Ogawa, S., Nakanishi, Y., Yamaga, Y., Yoshioka, T., Takaori, K., Uemoto, S., Saur, D., Chiba, T., & Seno, H. (2021). Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging. ELife, 10, e55117. https://doi.org/10.7554/eLife.55117 Cite
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Deciphering the Genomic and lncRNA Landscapes of Aerobic Glycolysis Identifies Potential Therapeutic Targets in Pancreatic Cancer

Integrated analysis of transcriptional profiles revealed many differentially expressed long non-coding RNAs involved in PDAC aerobic glycolysis.
[International Journal of Biological Sciences]
Zhu, L.-L., Wu, Z., Li, R.-K., Xing, X., Jiang, Y.-S., Li, J., Wang, Y.-H., Hu, L.-P., Wang, X., Qin, W.-T., Sun, Y.-W., Zhang, Z.-G., Yang, Q., & Jiang, S.-H. (2021). Deciphering the genomic and lncRNA landscapes of aerobic glycolysis identifies potential therapeutic targets in pancreatic cancer. International Journal of Biological Sciences, 17(1), 107–118. https://doi.org/10.7150/ijbs.49243 Cite
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S100A16 Promotes Metastasis and Progression of Pancreatic Cancer through FGF19-Mediated AKT and ERK1/2 Pathways

Researchers demonstrated that S100A16 promoted PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induced PDAC cell cycle arrest in the G2/M phase and apoptosis.
[Cell Biology and Toxicology]
Fang, D., Zhang, C., Xu, P., Liu, Y., Mo, X., Sun, Q., Abdelatty, A., Hu, C., Xu, H., Zhou, G., Xia, H., & Lan, L. (2021). S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways. Cell Biology and Toxicology. https://doi.org/10.1007/s10565-020-09574-w Cite
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The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy

Scientists determined the feasibility of Mucin 1 (MUC1)-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody.
[Cancers]
Hull, A., Li, Y., Bartholomeusz, D., Hsieh, W., Escarbe, S., Ruszkiewicz, A., & Bezak, E. (2021). The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy. Cancers, 13(1), 61. https://doi.org/10.3390/cancers13010061 Cite
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