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3. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts

Author

Eckert, Mark A, Coscia, Fabian, Chryplewicz, Agnieszka, Chang, Jae Won, Hernandez, Kyle M, Pan, Shawn, Tienda, Samantha M, Nahotko, Dominik A, Li, Gang, Blaženović, Ivana, Lastra, Ricardo R, Curtis, Marion, Yamada, S Diane, Perets, Ruth, McGregor, Stephanie M, Andrade, Jorge, Fiehn, Oliver, Moellering, Raymond E, Mann, Matthias, and Lengyel, Ernst

Subjects
Rare Diseases, Genetics, Ovarian Cancer, Biotechnology, Cancer, Aetiology, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Cancer-Associated Fibroblasts, Cell Line, Tumor, Cells, Cultured, DNA Methylation, Disease Progression, Female, Histones, Humans, Neoplasm Metastasis, Niacinamide, Nicotinamide N-Methyltransferase, Ovarian Neoplasms, Phenotype, Prognosis, Proteomics, S-Adenosylhomocysteine, S-Adenosylmethionine, General Science & Technology
Abstract

High-grade serous carcinoma has a poor prognosis, owing primarily to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer1,2, but a systematic examination of both the tumour and stromal compartments is critical in understanding ovarian cancer metastasis. Here we develop a label-free proteomic workflow to analyse as few as 5,000 formalin-fixed, paraffin-embedded cells microdissected from each compartment. The tumour proteome was stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and several of the proteins that it regulates. Stromal NNMT expression was necessary and sufficient for functional aspects of the cancer-associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT expression supported ovarian cancer migration, proliferation and in vivo growth and metastasis. Expression of NNMT in CAFs led to depletion of S-adenosyl methionine and reduction in histone methylation associated with widespread gene expression changes in the tumour stroma. This work supports the use of ultra-low-input proteomics to identify candidate drivers of disease phenotypes. NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma that may be therapeutically targeted.

Published
2019

9. Flower lose, a cell fitness marker, predicts COVID‐19 prognosis

Author

Yekelchyk, Michail, Madan, Esha, Wilhelm, Jochen, Short, Kirsty R, Palma, António M, Liao, Linbu, Camacho, Denise, Nkadori, Everlyne, Winters, Michael T, Rice, Emily S, Rolim, Inês, Cruz‐Duarte, Raquel, Pelham, Christopher J, Nagane, Masaki, Gupta, Kartik, Chaudhary, Sahil, Braun, Thomas, Pillappa, Raghavendra, Parker, Mark S, Menter, Thomas, Matter, Matthias, Haslbauer, Jasmin Dionne, Tolnay, Markus, Galior, Kornelia D, Matkwoskyj, Kristina A, McGregor, Stephanie M, Muller, Laura K, Rakha, Emad A, Lopez‐Beltran, Antonio, Drapkin, Ronny, Ackermann, Maximilian, Fisher, Paul B, Grossman, Steven R, Godwin, Andrew K, Kulasinghe, Arutha, Martinez, Ivan, Marsh, Clay B, Tang, Benjamin, Wicha, Max S, Won, Kyoung Jae, Tzankov, Alexandar, Moreno, Eduardo, and Gogna, Rajan

Published
2021
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20. Data from SPHK1 Is a Novel Target of Metformin in Ovarian Cancer

Author

Hart, Peter C., primary, Chiyoda, Tatsuyuki, primary, Liu, Xiaojing, primary, Weigert, Melanie, primary, Curtis, Marion, primary, Chiang, Chun-Yi, primary, Loth, Rachel, primary, Lastra, Ricardo, primary, McGregor, Stephanie M., primary, Locasale, Jason W., primary, Lengyel, Ernst, primary, and Romero, Iris L., primary

Published
2023
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22. Data from Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

Author

Hu, Yang, primary, Manasrah, Baraa K., primary, McGregor, Stephanie M., primary, Lera, Robert F., primary, Norman, Roshan X., primary, Tucker, John B., primary, Scribano, Christina M., primary, Yan, Rachel E., primary, Humayun, Mouhita, primary, Wisinski, Kari B., primary, Tevaarwerk, Amye J., primary, O'Regan, Ruth M., primary, Wilke, Lee G., primary, Weaver, Beth A., primary, Beebe, David J., primary, Jin, Ning, primary, and Burkard, Mark E., primary

Published
2023
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24. Data from Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention

Author

Chiyoda, Tatsuyuki, primary, Hart, Peter C., primary, Eckert, Mark A., primary, McGregor, Stephanie M., primary, Lastra, Ricardo R., primary, Hamamoto, Ryuji, primary, Nakamura, Yusuke, primary, Yamada, S. Diane, primary, Olopade, Olufunmilayo I., primary, Lengyel, Ernst, primary, and Romero, Iris L., primary

Published
2023
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26. Video 1 from Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

Author

Hu, Yang, primary, Manasrah, Baraa K., primary, McGregor, Stephanie M., primary, Lera, Robert F., primary, Norman, Roshan X., primary, Tucker, John B., primary, Scribano, Christina M., primary, Yan, Rachel E., primary, Humayun, Mouhita, primary, Wisinski, Kari B., primary, Tevaarwerk, Amye J., primary, O'Regan, Ruth M., primary, Wilke, Lee G., primary, Weaver, Beth A., primary, Beebe, David J., primary, Jin, Ning, primary, and Burkard, Mark E., primary

Published
2023
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27. Fig S6 from Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention

Author

Chiyoda, Tatsuyuki, primary, Hart, Peter C., primary, Eckert, Mark A., primary, McGregor, Stephanie M., primary, Lastra, Ricardo R., primary, Hamamoto, Ryuji, primary, Nakamura, Yusuke, primary, Yamada, S. Diane, primary, Olopade, Olufunmilayo I., primary, Lengyel, Ernst, primary, and Romero, Iris L., primary

Published
2023
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31. Supplementary Data from Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

Author

Hu, Yang, primary, Manasrah, Baraa K., primary, McGregor, Stephanie M., primary, Lera, Robert F., primary, Norman, Roshan X., primary, Tucker, John B., primary, Scribano, Christina M., primary, Yan, Rachel E., primary, Humayun, Mouhita, primary, Wisinski, Kari B., primary, Tevaarwerk, Amye J., primary, O'Regan, Ruth M., primary, Wilke, Lee G., primary, Weaver, Beth A., primary, Beebe, David J., primary, Jin, Ning, primary, and Burkard, Mark E., primary

Published
2023
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33. Supplementary Figure Legends from Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention

Author

Chiyoda, Tatsuyuki, primary, Hart, Peter C., primary, Eckert, Mark A., primary, McGregor, Stephanie M., primary, Lastra, Ricardo R., primary, Hamamoto, Ryuji, primary, Nakamura, Yusuke, primary, Yamada, S. Diane, primary, Olopade, Olufunmilayo I., primary, Lengyel, Ernst, primary, and Romero, Iris L., primary

Published
2023
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35. Video 2 from Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

Author

Hu, Yang, primary, Manasrah, Baraa K., primary, McGregor, Stephanie M., primary, Lera, Robert F., primary, Norman, Roshan X., primary, Tucker, John B., primary, Scribano, Christina M., primary, Yan, Rachel E., primary, Humayun, Mouhita, primary, Wisinski, Kari B., primary, Tevaarwerk, Amye J., primary, O'Regan, Ruth M., primary, Wilke, Lee G., primary, Weaver, Beth A., primary, Beebe, David J., primary, Jin, Ning, primary, and Burkard, Mark E., primary

Published
2023
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39. Spatial Alignment of Organoids Tracking Subclonal Chemotherapy Resistance in Pancreatic and Ampullary Cancer

Author

Hossan, Md Shahadat, primary, Lin, Ethan Samuel, additional, Riedl, Eleanor, additional, Stram, Austin, additional, Mehlhaff, Eric, additional, Koeppel, Luke, additional, Warner, Jamie, additional, Uko, Inem, additional, Mankowski Gettle, Lori, additional, Lubner, Sam, additional, McGregor, Stephanie M., additional, Zhang, Wei, additional, Murphy, William, additional, and Kratz, Jeremy D., additional

Published
2023
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43. Efficacy of Topically Administered Dihydroartemisinin in Treating Papillomavirus-Induced Anogenital Dysplasia in Preclinical Mouse Models

Author

Gunder, Laura C., primary, Blaine-Sauer, Simon, additional, Johnson, Hillary R., additional, Shin, Myeong-Kyun, additional, Auyeung, Andrew S., additional, Zhang, Wei, additional, Leverson, Glen E., additional, Ward-Shaw, Ella T., additional, King, Renee E., additional, McGregor, Stephanie M., additional, Matkowskyj, Kristina A., additional, Lambert, Paul F., additional, and Carchman, Evie H., additional

Published
2022
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45. Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer

Author

Hu, Yang, primary, Manasrah, Baraa K., additional, McGregor, Stephanie M., additional, Lera, Robert F., additional, Norman, Roshan X., additional, Tucker, John B., additional, Scribano, Christina M., additional, Yan, Rachel E., additional, Humayun, Mouhita, additional, Wisinski, Kari B., additional, Tevaarwerk, Amye J., additional, O'Regan, Ruth M., additional, Wilke, Lee G., additional, Weaver, Beth A., additional, Beebe, David J., additional, Jin, Ning, additional, and Burkard, Mark E., additional

Published
2021
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46. Mammary Tumor Growth and Proliferation Are Dependent on Growth Hormone in Female SV40 C3(1) T-Antigen Mice.

Author

Unterberger, Christopher J, McGregor, Stephanie M, Kopchick, John J, Swanson, Steven M, and Marker, Paul C

Abstract

Female SV40 C3(1) T-antigen (C3(1)/TAg) transgenic mice develop mammary tumors that are molecularly similar to human basal-like breast cancers with 100% incidence at 16 weeks of age. To determine the requirement for growth hormone (GH) signaling in these tumors, genetic crosses were used to create cohorts of female mice that were homozygous for a floxed growth hormone receptor (Ghr) gene and carried one copy each of the Rosa-Cre-ERT2 transgene and the C3(1)/TAg transgene (Ghr flox/flox; Rosa-Cre-ERT2; C3(1)/TAg+/0 mice). When the largest mammary tumor reached 200 mm3, mice were treated with tamoxifen to delete Ghr or with vehicle as a control. An additional group of Ghr flox/flox; C3(1)/TAg+/0 mice were also treated with tamoxifen when the largest mammary tumor reached 200 mm3 as a control for the effects of tamoxifen. After 3 weeks, tumors in mice in which Ghr was deleted began to shrink while vehicle and tamoxifen treatment control mouse tumors continued to grow. Pathological analysis of tumors revealed similar growth patterns and varying levels of necrosis throughout all groups. A decrease in cancer cell proliferation in Ghr-/- tumors relative to controls was observed as measured by Ki67 immunohistochemistry labeling index. These data suggest that even established C3(1)/TAg mammary tumors are dependent on the GH/IGF-1 axis. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel

Author

Scribano, Christina M., primary, Wan, Jun, additional, Esbona, Karla, additional, Tucker, John B., additional, Lasek, Amber, additional, Zhou, Amber S., additional, Zasadil, Lauren M., additional, Molini, Ryan, additional, Fitzgerald, Jonathan, additional, Lager, Angela M., additional, Laffin, Jennifer J., additional, Correia-Staudt, Kayla, additional, Wisinski, Kari B., additional, Tevaarwerk, Amye J., additional, O’Regan, Ruth, additional, McGregor, Stephanie M., additional, Fowler, Amy M., additional, Chappell, Richard J., additional, Bugni, Tim S., additional, Burkard, Mark E., additional, and Weaver, Beth A., additional

Published
2021
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48. sj-pdf-1-jhc-10.1369_00221554211061359 ��� Supplemental material for Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas

Author

Renner, Carine, Gomez, Clarissa, Visetsouk, Mike R., Taha, Isra, Khan, Aisha, McGregor, Stephanie M., Weisman, Paul, Naba, Alexandra, Masters, Kristyn S., and Kreeger, Pamela K.

Subjects
FOS: Biological sciences, FOS: Clinical medicine, Cell Biology, 69999 Biological Sciences not elsewhere classified, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental material, sj-pdf-1-jhc-10.1369_00221554211061359 for Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas by Carine Renner, Clarissa Gomez, Mike R. Visetsouk, Isra Taha, Aisha Khan, Stephanie M. McGregor, Paul Weisman, Alexandra Naba, Kristyn S. Masters and Pamela K. Kreeger in Journal of Histochemistry & Cytochemistry

Published
2021
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49. sj-docx-6-jhc-10.1369_00221554211061359 ��� Supplemental material for Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas

Author

Renner, Carine, Gomez, Clarissa, Visetsouk, Mike R., Taha, Isra, Khan, Aisha, McGregor, Stephanie M., Weisman, Paul, Naba, Alexandra, Masters, Kristyn S., and Kreeger, Pamela K.

Subjects
FOS: Biological sciences, FOS: Clinical medicine, Cell Biology, 69999 Biological Sciences not elsewhere classified, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Abstract

Supplemental material, sj-docx-6-jhc-10.1369_00221554211061359 for Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas by Carine Renner, Clarissa Gomez, Mike R. Visetsouk, Isra Taha, Aisha Khan, Stephanie M. McGregor, Paul Weisman, Alexandra Naba, Kristyn S. Masters and Pamela K. Kreeger in Journal of Histochemistry & Cytochemistry

Published
2021
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