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282 results on '"Freemantle, Sarah J."'

1. Perfluorooctanesulfonic Acid Alters Pro-Cancer Phenotypes and Metabolic and Transcriptional Signatures in Testicular Germ Cell Tumors.

Author

Boyd, Raya I., Shokry, Doha, Fazal, Zeeshan, Rennels, Brayden C., Freemantle, Sarah J., La Frano, Michael R., Prins, Gail S., Madak Erdogan, Zeynep, Irudayaraj, Joseph, Singh, Ratnakar, and Spinella, Michael J.

Subjects
PERFLUOROOCTANE sulfonate, GERM cell tumors, PHENOTYPES, FLUOROALKYL compounds, EPIGENOMICS, GENETIC regulation
Abstract

The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recently emergent human and environmental health concern. There is a consistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is relatively strong evidence linking PFAS and testicular germ cell tumors (TGCTs). However, no mechanistic studies have been performed to date concerning PFAS and TGCTs. In this report, the effects of the legacy PFAS perfluorooctanesulfonic acid (PFOS) and the newer "clean energy" PFAS lithium bis(trifluoromethylsulfonyl)imide (LiTFSi, called HQ-115), on the tumorigenicity of TGCTs in mice, TGCT cell survival, and metabolite production, as well as gene regulation were investigated. In vitro, the proliferation and survival of both chemo-sensitive and -resistant TGCT cells were minimally affected by a wide range of PFOS and HQ-115 concentrations. However, both chemicals promoted the growth of TGCT cells in mouse xenografts at doses consistent with human exposure but induced minimal acute toxicity, as assessed by total body, kidney, and testis weight. PFOS, but not HQ-115, increased liver weight. Transcriptomic alterations of PFOS-exposed normal mouse testes were dominated by cancer-related pathways and gene expression alterations associated with the H3K27me3 polycomb pathway and DNA methylation, epigenetic pathways that were previously showed to be critical for the survival of TGCT cells after cisplatin-based chemotherapy. Similar patterns of PFOS-mediated gene expression occurred in PFOS-exposed cells in vitro. Metabolomic studies revealed that PFOS also altered metabolites associated with steroid biosynthesis and fatty acid metabolism in TGCT cells, consistent with the proposed ability of PFAS to mimic fatty acid-based ligands controlling lipid metabolism and the proposed role of PFAS as endocrine disrupters. Our data, is the first cell and animal based study on PFAS in TGCTs, support a pro-tumorigenic effect of PFAS on TGCT biology and suggests epigenetic, metabolic, and endocrine disruption as potential mechanisms of action that are consistent with the non-mutagenic nature of the PFAS class. [ABSTRACT FROM AUTHOR]

Published
2024
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2. G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells

Author

Corbet, Andrea K., primary, Bikorimana, Emmanuel, additional, Boyd, Raya I., additional, Shokry, Doha, additional, Kries, Kelly, additional, Gupta, Ayush, additional, Paton, Anneliese, additional, Sun, Zhengyang, additional, Fazal, Zeeshan, additional, Freemantle, Sarah J., additional, Nelson, Erik R., additional, Spinella, Michael J., additional, and Singh, Ratnakar, additional

Published
2023
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3. Supplementary table from A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers

Author

Kawakami, Masanori, primary, Mustachio, Lisa Maria, primary, Chen, Yulong, primary, Chen, Zibo, primary, Liu, Xiuxia, primary, Wei, Cheng-Hsin, primary, Roszik, Jason, primary, Kittai, Adam S., primary, Danilov, Alexey V., primary, Zhang, Xiaoshan, primary, Fang, Bingliang, primary, Wang, Jing, primary, Heymach, John V., primary, Tyutyunyk-Massey, Liliya, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Liu, Xi, primary, and Dmitrovsky, Ethan, primary

Published
2023
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4. Data from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Author

Dragnev, Konstantin H., primary, Ma, Tian, primary, Cyrus, Jobin, primary, Galimberti, Fabrizio, primary, Memoli, Vincent, primary, Busch, Alexander M., primary, Tsongalis, Gregory J., primary, Seltzer, Marc, primary, Johnstone, David, primary, Erkmen, Cherie P., primary, Nugent, William, primary, Rigas, James R., primary, Liu, Xi, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Waxman, Samuel, primary, and Dmitrovsky, Ethan, primary

Published
2023
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5. Supplementary Figures 1-6 from The Ubiquitin-Specific Peptidase USP18 Promotes Lipolysis, Fatty Acid Oxidation, and Lung Cancer Growth

Author

Liu, Xi, primary, Lu, Yun, primary, Chen, Zibo, primary, Liu, Xiuxia, primary, Hu, Weiguo, primary, Zheng, Lin, primary, Chen, Yulong, primary, Kurie, Jonathan M., primary, Shi, Mi, primary, Mustachio, Lisa Maria, primary, Adresson, Thorkell, primary, Fox, Stephen, primary, Roszik, Jason, primary, Kawakami, Masanori, primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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6. supplementary figure and legend from Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2

Author

Danilov, Alexey V., primary, Hu, Shanhu, primary, Orr, Bernardo, primary, Godek, Kristina, primary, Mustachio, Lisa Maria, primary, Sekula, David, primary, Liu, Xi, primary, Kawakami, Masanori, primary, Johnson, Faye M., primary, Compton, Duane A., primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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7. Data from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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8. Supplemental Figures 1-10 from Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer

Author

Mustachio, Lisa Maria, primary, Lu, Yun, primary, Tafe, Laura J., primary, Memoli, Vincent, primary, Rodriguez-Canales, Jaime, primary, Mino, Barbara, primary, Villalobos, Pamela Andrea, primary, Wistuba, Ignacio, primary, Katayama, Hiroyuki, primary, Hanash, Samir M., primary, Roszik, Jason, primary, Kawakami, Masanori, primary, Cho, Kwang-jin, primary, Hancock, John F., primary, Chinyengetere, Fadzai, primary, Hu, Shanhu, primary, Liu, Xi, primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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9. Supplementary Text and Legends from Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer

Author

Mustachio, Lisa Maria, primary, Lu, Yun, primary, Tafe, Laura J., primary, Memoli, Vincent, primary, Rodriguez-Canales, Jaime, primary, Mino, Barbara, primary, Villalobos, Pamela Andrea, primary, Wistuba, Ignacio, primary, Katayama, Hiroyuki, primary, Hanash, Samir M., primary, Roszik, Jason, primary, Kawakami, Masanori, primary, Cho, Kwang-jin, primary, Hancock, John F., primary, Chinyengetere, Fadzai, primary, Hu, Shanhu, primary, Liu, Xi, primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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10. Video-Supplementary Fig. 2a from Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2

Author

Danilov, Alexey V., primary, Hu, Shanhu, primary, Orr, Bernardo, primary, Godek, Kristina, primary, Mustachio, Lisa Maria, primary, Sekula, David, primary, Liu, Xi, primary, Kawakami, Masanori, primary, Johnson, Faye M., primary, Compton, Duane A., primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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11. Supplementary Figure 1 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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12. Supplementary Figure S1 from Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models

Author

Dragnev, Konstantin H., primary, Ma, Tian, primary, Cyrus, Jobin, primary, Galimberti, Fabrizio, primary, Memoli, Vincent, primary, Busch, Alexander M., primary, Tsongalis, Gregory J., primary, Seltzer, Marc, primary, Johnstone, David, primary, Erkmen, Cherie P., primary, Nugent, William, primary, Rigas, James R., primary, Liu, Xi, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Waxman, Samuel, primary, and Dmitrovsky, Ethan, primary

Published
2023
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13. Data from A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers

Author

Kawakami, Masanori, primary, Mustachio, Lisa Maria, primary, Chen, Yulong, primary, Chen, Zibo, primary, Liu, Xiuxia, primary, Wei, Cheng-Hsin, primary, Roszik, Jason, primary, Kittai, Adam S., primary, Danilov, Alexey V., primary, Zhang, Xiaoshan, primary, Fang, Bingliang, primary, Wang, Jing, primary, Heymach, John V., primary, Tyutyunyk-Massey, Liliya, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Liu, Xi, primary, and Dmitrovsky, Ethan, primary

Published
2023
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14. Supplementary Figure 5 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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15. Supplementary Figure 2 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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16. Supplementary Fig. 2. from Dinaciclib Induces Anaphase Catastrophe in Lung Cancer Cells via Inhibition of Cyclin-Dependent Kinases 1 and 2

Author

Danilov, Alexey V., primary, Hu, Shanhu, primary, Orr, Bernardo, primary, Godek, Kristina, primary, Mustachio, Lisa Maria, primary, Sekula, David, primary, Liu, Xi, primary, Kawakami, Masanori, primary, Johnson, Faye M., primary, Compton, Duane A., primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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17. Supplementary Figure 1 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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18. Data from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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19. Supplementary Figure 4 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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20. Data from The Ubiquitin-Specific Peptidase USP18 Promotes Lipolysis, Fatty Acid Oxidation, and Lung Cancer Growth

Author

Liu, Xi, primary, Lu, Yun, primary, Chen, Zibo, primary, Liu, Xiuxia, primary, Hu, Weiguo, primary, Zheng, Lin, primary, Chen, Yulong, primary, Kurie, Jonathan M., primary, Shi, Mi, primary, Mustachio, Lisa Maria, primary, Adresson, Thorkell, primary, Fox, Stephen, primary, Roszik, Jason, primary, Kawakami, Masanori, primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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21. Supplementary Figure Legend from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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22. Data from Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer

Author

Mustachio, Lisa Maria, primary, Lu, Yun, primary, Tafe, Laura J., primary, Memoli, Vincent, primary, Rodriguez-Canales, Jaime, primary, Mino, Barbara, primary, Villalobos, Pamela Andrea, primary, Wistuba, Ignacio, primary, Katayama, Hiroyuki, primary, Hanash, Samir M., primary, Roszik, Jason, primary, Kawakami, Masanori, primary, Cho, Kwang-jin, primary, Hancock, John F., primary, Chinyengetere, Fadzai, primary, Hu, Shanhu, primary, Liu, Xi, primary, Freemantle, Sarah J., primary, and Dmitrovsky, Ethan, primary

Published
2023
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24. Supplementary Figure 6 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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25. Supplementary Figure 7 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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26. Supplementary Figure 3 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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27. Supplementary figures from A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers

Author

Kawakami, Masanori, primary, Mustachio, Lisa Maria, primary, Chen, Yulong, primary, Chen, Zibo, primary, Liu, Xiuxia, primary, Wei, Cheng-Hsin, primary, Roszik, Jason, primary, Kittai, Adam S., primary, Danilov, Alexey V., primary, Zhang, Xiaoshan, primary, Fang, Bingliang, primary, Wang, Jing, primary, Heymach, John V., primary, Tyutyunyk-Massey, Liliya, primary, Freemantle, Sarah J., primary, Kurie, Jonathan M., primary, Liu, Xi, primary, and Dmitrovsky, Ethan, primary

Published
2023
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28. Supplementary Figure Legend from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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29. Supplementary Figure 3 from Comparing Histone Deacetylase Inhibitor Responses in Genetically Engineered Mouse Lung Cancer Models and a Window of Opportunity Trial in Patients with Lung Cancer

Author

Ma, Tian, primary, Galimberti, Fabrizio, primary, Erkmen, Cherie P., primary, Memoli, Vincent, primary, Chinyengetere, Fadzai, primary, Sempere, Lorenzo, primary, Beumer, Jan H., primary, Anyang, Bean N., primary, Nugent, William, primary, Johnstone, David, primary, Tsongalis, Gregory J., primary, Kurie, Jonathan M., primary, Li, Hua, primary, DiRenzo, James, primary, Guo, Yongli, primary, Freemantle, Sarah J., primary, Dragnev, Konstantin H., primary, and Dmitrovsky, Ethan, primary

Published
2023
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30. Supplementary Figure 2 from Evidence for the Ubiquitin Protease UBP43 as an Antineoplastic Target

Author

Guo, Yongli, primary, Chinyengetere, Fadzai, primary, Dolinko, Andrey V., primary, Lopez-Aguiar, Alexandra, primary, Lu, Yun, primary, Galimberti, Fabrizio, primary, Ma, Tian, primary, Feng, Qing, primary, Sekula, David, primary, Freemantle, Sarah J., primary, Andrew, Angeline S., primary, Memoli, Vincent, primary, and Dmitrovsky, Ethan, primary

Published
2023
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32. Supplementary Data from Uncovering Growth-Suppressive MicroRNAs in Lung Cancer

Author

Liu, Xi, primary, Sempere, Lorenzo F., primary, Galimberti, Fabrizio, primary, Freemantle, Sarah J., primary, Black, Candice, primary, Dragnev, Konstantin H., primary, Ma, Yan, primary, Fiering, Steven, primary, Memoli, Vincent, primary, Li, Hua, primary, DiRenzo, James, primary, Korc, Murray, primary, Cole, Charles N., primary, Bak, Mads, primary, Kauppinen, Sakari, primary, and Dmitrovsky, Ethan, primary

Published
2023
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39. The Retinoids and Cancer Chemoprevention

Author

Kitareewan, Sutisak, Pitha-Rowe, Ian, Ma, Yan, Freemantle, Sarah J., Dmitrovsky, Ethan, Teicher, Beverly A., editor, Kelloff, Gary J., editor, Hawk, Ernest T., editor, and Sigman, Caroline C., editor

Published
2004
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42. Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy

Author

Singh, Ratnakar, primary, Fazal, Zeeshan, additional, Bikorimana, Emmanuel, additional, Boyd, Raya I., additional, Yerby, Cliff, additional, Tomlin, Megan, additional, Baldwin, Hannah, additional, Shokry, Doha, additional, Corbet, Andrea K., additional, Shahid, Khadeeja, additional, Hattab, Aleyah, additional, Freemantle, Sarah J., additional, and Spinella, Michael J., additional

Published
2021
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43. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

Author

Liu, Xi, Sempere, Lorenzo F., Ouyang, Haoxu, Memoli, Vincent A., Andrew, Angeline S., Luo, Yue, Demidenko, Eugene, Korc, Murray, Shi, Wei, Preis, Meir, Dragnev, Konstantin H., Li, Hua, DiRenzo, James, Bak, Mads, Freemantle, Sarah J., Kauppinen, Sakari, and Dmitrovsky, Ethan

Subjects
Gene expression -- Physiological aspects -- Genetic aspects -- Research, MicroRNA -- Properties -- Physiological aspects -- Research -- Genetic aspects, Lung cancer -- Development and progression -- Care and treatment -- Research -- Genetic aspects, Cancer cells -- Genetic aspects -- Physiological aspects -- Research, Oncology -- Research -- Physiological aspects, Health care industry
Abstract

Micro RNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microar-ray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31-mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression., Introduction MicroRNAs (miRNAs) are critical regulators of gene expression (1), (2). Mature miRNAs bind target mRNAs at complementary sites in 3'-untranslated regions (3'-UTRs) or coding sequences and thereby trigger downregulation, [...]

Published
2010
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45. A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers

Author

Kawakami, Masanori, primary, Mustachio, Lisa Maria, additional, Chen, Yulong, additional, Chen, Zibo, additional, Liu, Xiuxia, additional, Wei, Cheng-Hsin, additional, Roszik, Jason, additional, Kittai, Adam S., additional, Danilov, Alexey V., additional, Zhang, Xiaoshan, additional, Fang, Bingliang, additional, Wang, Jing, additional, Heymach, John V., additional, Tyutyunyk-Massey, Liliya, additional, Freemantle, Sarah J., additional, Kurie, Jonathan M., additional, Liu, Xi, additional, and Dmitrovsky, Ethan, additional

Published
2021
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46. TRIGGERING ANAPHASE CATASTROPHE TO COMBAT ANEUPLOID CANCERS

Author

DMITROVSKY, ETHAN, KAWAKAMI, MASANORI, LIU, XI, FREEMANTLE, SARAH J., and KURIE, JONATHAN M.

Subjects
Articles
Abstract

Cancer cells are genetically unstable and often have supernumerary centrosomes. When supernumerary centrosome clustering is inhibited at mitosis, multipolar cell division is forced, triggering apoptosis in daughter cells. This proapoptotic pathway is called anaphase catastrophe. Cyclin-dependent kinase 1 (CDK1) or CDK2 inhibitors can antagonize centrosome clustering and cause anaphase catastrophe to occur in lung cancer and other types of cancer. The centrosome protein CP110, a CDK1 and CDK2 phosphorylation substrate, engages anaphase catastrophe. Intriguingly, CP110 is downregulated by the KRAS oncoprotein, enhancing sensitivity of KRAS-driven cancers to CDK2 inhibitors. Anaphase catastrophe eradicates aneuploid cancer cells while relatively sparing normal diploid cells with two centrosomes. This therapeutic window discriminates between normal and neoplastic cells and can be exploited in the cancer clinic. The work reviewed here establishes that pharmacologically-induced anaphase catastrophe is useful to combat aneuploid cancers, especially when the KRAS oncoprotein is activated. This addresses an unmet medical need in oncology.

Published
2020

47. The Ubiquitin-Specific Peptidase USP18 Promotes Lipolysis, Fatty Acid Oxidation, and Lung Cancer Growth

Author

Liu, Xi, primary, Lu, Yun, additional, Chen, Zibo, additional, Liu, Xiuxia, additional, Hu, Weiguo, additional, Zheng, Lin, additional, Chen, Yulong, additional, Kurie, Jonathan M., additional, Shi, Mi, additional, Mustachio, Lisa Maria, additional, Adresson, Thorkell, additional, Fox, Stephen, additional, Roszik, Jason, additional, Kawakami, Masanori, additional, Freemantle, Sarah J., additional, and Dmitrovsky, Ethan, additional

Published
2020
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48. Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours

Author

Fazal, Zeeshan, primary, Singh, Ratnakar, additional, Fang, Fang, additional, Bikorimana, Emmanuel, additional, Baldwin, Hannah, additional, Corbet, Andrea, additional, Tomlin, Megan, additional, Yerby, Cliff, additional, Adra, Nabil, additional, Albany, Costantine, additional, Lee, Sarah, additional, Freemantle, Sarah J., additional, Nephew, Kenneth P, additional, Christensen, Brock C, additional, and Spinella, Michael J., additional

Published
2020
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