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  • 1
    Online Resource
    Online Resource
    Erratum: Corrigendum: A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate
    Springer Science and Business Media LLC ; 2016
    In:  Nature Chemical Biology Vol. 12, No. 8 ( 2016-8), p. 656-656
    Details
    In: Nature Chemical Biology, Springer Science and Business Media LLC, Vol. 12, No. 8 ( 2016-8), p. 656-656
    Type of Medium: Online Resource
    ISSN: 1552-4450 , 1552-4469
    URL: Article
    DOI: 10.1038/nchembio0816-656
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2190276-8
    SSG: 12
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Abstract A43: Loss of Keap1 promotes KRAS-driven lung cancer and results in genotype-specific vulnerabilities
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 10_Supplement ( 2018-05-15), p. A43-A43
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 10_Supplement ( 2018-05-15), p. A43-A43
    Abstract: Treating KRAS mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein1. One approach to addressing this challenge is to define frequently co-occurring mutations with KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS mutant LUAD tumors carry loss-of-function (LOF) mutations in Kelch-like ECH-associated protein 1 (KEAP1)2-4, a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response5-10. The high frequency of mutations in KEAP1, which would be predicted to result in activation of the NRF2 pathway, suggests an important role for the oxidative stress response in lung tumorigenesis. To test this directly, we used a CRISPR/Cas9-based approach in a mouse model of Kras-driven LUAD to examine the effects of loss of KEAP1 function in lung cancer progression. We show that loss of KEAP1 hyper-activates Nrf2 and promotes Kras-driven LUAD. Combining CRISPR/Cas9-based genetic screening and metabolomic analyses, we also show that KEAP1/NRF2 mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacologic inhibition of glutaminase. Finally, we provide a rationale for sub-stratification of human lung cancer patients with KRAS-KEAP1 or -NRF2 mutant tumors as likely to respond to glutaminase inhibition. Citation Format: Rodrigo Romero, Volkan I. Sayin, Davidson M. Shawn, Matthew Bauer, Simranjit X. Singh, Sarah LeBoeuf, Triantafyllia R. Karakousi, Donald C. Ellis, Arjun Bhutkar, Francisco Sanchez-Rivera, Lakshmipriya Subbaraj, Britney Martinez, Roderick T. Bronson, Justin R. Prigge, Edward E. Schmidt, Craig J. Thomas, Angela Davies, Igor Dolgalev, Adriana Heguy, Viola Allaj, John T. Piorier, Andre L. Moreira, Charles M. Rudin, Harvey I. Pass, Matthew G. Vander Heiden, Tyler Jacks, Thales Papagiannakopoulos. Loss of Keap1 promotes KRAS-driven lung cancer and results in genotype-specific vulnerabilities [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A43.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.MOUSEMODELS17-A43
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 3
    Online Resource
    Online Resource
    Abstract 5989: Metabolic heterogeneity of the tumor microenvironment
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5989-5989
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 5989-5989
    Abstract: Background: Single cell technologies have provided insight into the cellular and phenotypic heterogeneity of the tumor microenvironment (TME). However, major technical hurdles exist to elucidate the metabolic fate of a given metabolite in the cellularly diverse TME. Methods: By collecting tumor interstitial fluid from human kidney tumors and matched normal tissue, our group has gained valuable insight into the metabolic content of the Renal Cell Carcinoma microenvironment and the normal kidney parenchyma. Given the high concentration of glucose in both of these tissue environments ( & gt;4 mM), we hypothesized that infiltrating immune cells and transformed cells can use this widely available sugar as a fuel source. To test this hypothesis, we labeled glycolytic cells in the tumor microenvironment using the widely clinically adopted F18 fluoro-2-deoxyglucose (FDG) Positron Emission Tomography (PET) tracer. By conducting successive magnetic bead separation, highly enriched immune cell and non-immune cell fractions were analyzed for radioactive, transcriptomic and metabolic analysis. Results: This work has led to the intriguing discovery that infiltrating CD45+ immune cells are more actively glucose consuming than CD45- tumor cells on a per cell basis. Additionally, even though these cells make up a minority of the population of the entire TME ( & lt;15%), they contribute to & gt; 65% of the total glucose uptake in the tumor microenvironment. Subsequent metabolic studies have shown that they are also more actively glycolytic. This phenomenon holds true across multiple orthotopic tumor models in multiple mouse genetic backgrounds. Further characterization of this glycolytic CD45+ fraction illustrates that the CD11b+, F4/80+ tumor associated macrophages (TAM) fraction is the most avid. Additionally, the tumor infiltrating T cells have much higher FDG avidity than the naïve splenocytes and surprisingly the transformed cancer cells. In support of this data, ex vivo seahorse analysis using these fractions demonstrates that the most metabolically active fraction is TAM-rich F4/80+ fraction. Infiltrating CD45+ cells appear to be metabolically fixed, as demonstrated by their lack of glycolytic reserve when compared to transformed tumor cells in the glycostress test. In order to examine the immunogenicity of F18 based tracers, we have traced the fate of F18-Glutamine (Q). Interestingly, the F18-Q accumulates to a much greater extent in the CD45- cells (on a per cell basis), illustrating the anaplerotic need of cancer cells. Conclusion: Ultimately, this work reveals the nutrient environment of the tumor interstitial space at a resolution not previously revealed, and uncovers the diversity of metabolic utilization across cell types in the heterogenous tumor microenvironment. Citation Format: Bradley I. Reinfeld, Matthew Z. Madden, Ahmed Ali, Melissa M. Wolf, Kirsten L. Young, Racheal Hongo, Kathryn E. Beckermann, Matthew G. Vander Heiden, Alex Muir, Jeffrey C. Rathmell, W. Kimryn Rathmell. Metabolic heterogeneity of the tumor microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5989.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-5989
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 4
    Online Resource
    Online Resource
    A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
    Springer Science and Business Media LLC ; 2014
    In:  Nature Communications Vol. 5, No. 1 ( 2014-04-03)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 5, No. 1 ( 2014-04-03)
    Abstract: Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/ncomms4608
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
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  • 5
    Online Resource
    Online Resource
    Abstract 90: Fatty acid synthesis is required for breast cancer brain metastasis
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 90-90
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 90-90
    Abstract: Brain metastases are refractory to therapies that otherwise control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the unique brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for breast cancer growth in the brain microenvironment may also introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors growing in the brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in the brain. We determine that this phenotype is an adaptation to decreased lipid availability in the brain relative to other tissues, which results in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies. Citation Format: Gino B. Ferraro, Ahmed Ali, Alba Luengo, David P. Kodack, Amy Deik, Keene L. Abbott, Divya Bezwada, Landry Blanc, Brendan Prideaux, Xin Jin, Jessica M. Possada, Jiang Chen, Christopher R. Chin, Zohreh Amoozgar, Raphael Ferreira, Ivy Chen, Kamila Naxerova, Christopher Ng, Anna M. Westermark, Mark Duquette, Sylvie Roberge, Costas A. Lyssiotis, Dan G. Duda, Todd R. Golub, Shawn M. Davidson, Dai Fukumura, Véronique A. Dartois, Clary B. Clish, Matthew G. Vander Heiden, Rakesh K. Jain. Fatty acid synthesis is required for breast cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 90.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-90
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Heterogeneity of tumor-induced gene expression changes in the human metabolic network
    Springer Science and Business Media LLC ; 2013
    In:  Nature Biotechnology Vol. 31, No. 6 ( 2013-6), p. 522-529
    Details
    In: Nature Biotechnology, Springer Science and Business Media LLC, Vol. 31, No. 6 ( 2013-6), p. 522-529
    Type of Medium: Online Resource
    ISSN: 1087-0156 , 1546-1696
    URL: Article
    DOI: 10.1038/nbt.2530
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 1494943-X
    detail.hit.zdb_id: 1311932-1
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Abstract PR04: Germline loss of PK-M2 promotes metabolic syndrome and hepatocellular carcinoma
    American Association for Cancer Research (AACR) ; 2016
    In:  Molecular Cancer Research Vol. 14, No. 4_Supplement ( 2016-04-01), p. PR04-PR04
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 4_Supplement ( 2016-04-01), p. PR04-PR04
    Abstract: The pyruvate kinase gene, Pkm, encodes the PK-M1 and PK-M2 isoforms, which are the result of alternative splicing of mutually exclusive exons. While PK-M1 is considered the adult pyruvate kinase isoform, PK-M2 has been closely linked to embryogenesis, tissue regeneration, stem cells, and cancer. Nonetheless, expression of PK-M2 is widespread in wild-type embryonic and adult tissues. To interrogate the functional requirement for PK-M2, we generated and characterized germline PK-M2 null mice (Pkm2-/-). We found that Pkm2-/- mice are viable and express PK-M1 throughout embryogenesis and into adulthood. Strikingly, PK-M2 loss leads to spontaneous hepatocellular carcinoma (HCC) that is preceded by progressive metabolic disease characterized by insulin resistance, inflammation, and hepatic steatosis. Therefore, in contrast to its role in modulating metabolism to promote cancer in a cell-intrinsic manner, PK-M2 plays a role in maintaining systemic metabolism, thereby preventing metabolic syndrome and HCC. To further dissect the contrasting systemic and cell-intrinsic roles of PK-M2 in the context of cancer, we have combined autochthonous mouse models of cancer from our lab with both the germline null allele of Pkm2, Pkm2-/-, and the conditional allele of Pkm2, Pkm2fl/fl. This study will allow us to elucidate the distinct cell-intrinsic and cell-extrinsic roles of PK-M2 in both maintaining normal systemic metabolism and aberrant proliferation in the context of cancer. This abstract is also presented as Poster B25. Citation Format: Talya L. Dayton, Vasilena Gocheva, Kathryn M. Miller, William J. Israelsen, Clary B. Clish, Arjun Bhutkar, Shawn M. Davidson, Alba Luengo, Matthew G. Vander Heiden, Tyler E. Jacks. Germline loss of PK-M2 promotes metabolic syndrome and hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr PR04.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1557-3125.DEVBIOLCA15-PR04
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2097884-4
    SSG: 12
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  • 8
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    Online Resource
    Abstract B06: The angiotensin receptor blocker and partial PPARγ agonist telmisartan inhibits the growth of pancreatic ductal adenocarcinoma
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 24_Supplement ( 2019-12-15), p. B06-B06
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 24_Supplement ( 2019-12-15), p. B06-B06
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to chemotherapy, partly due to the presence of a dense-fibrotic stroma and adaptive metabolism. Telmisartan is an angiotensin II type receptor 1 (AT1) antagonist with partial peroxisome proliferator-activated receptor gamma (PPARγ) agonistic activity used for treatment of hypertension. The aim of this study was to determine the effects of telmisartan on the viability of PDAC cells and tumor progression. In panels of 4 murine and 8 human PDAC cells, the telmisartan IC50 was lower in cells with a low steady-state expression of PPARγ and a mesenchymal cell morphology. In contrast, losartan—a selective AT1 inhibitor—did not affect the viability of PDAC cells. The siRNA knockdown of PPARγ enhanced the sensitivity of telmisartan and stimulated epithelial-mesenchymal transition, which was accompanied by an increase in Wnt signaling. PPARγ regulates glucose metabolism and autophagy. We thus assessed effects of telmisartan on bioenergetics and autophagy of PDAC cells. In PPARγ-knockdown and -scrambled cells telmisartan significantly reduced glucose uptake, without affecting ATP production, but increased respiratory capacity, which can maintain the production of ATP during hypoglycemia. Immunoblotting revealed that PPARγ knockdown compared to scramble cells had increased levels of phosphorylated-AMP-activated protein kinase (p-AMPK) and increased expression of LC3A/B—structural proteins of autophagosomal membranes—which implies higher levels of autophagy. We also compared effects of telmisartan treatment on LC3A/B expression to well-established autophagy modulators, chloroquine and verapamil. Under nutrient-rich conditions and as expected, chloroquine and verapamil treatment induced LC3A/B accumulation, consistent with active autophagic flux in these cells. Telmisartan treatment decreased the levels of LC3A/B in both scramble and PPARγ knockdown cells and decreased the formation of LC3A/B positive granules in other PDAC cell lines. Telmisartan can also induce the accumulation of the signal adaptor protein p62 (SQSTM1), even in the presence of verapamil, which is also consistent with autophagy inhibition. Telmisartan did not prevent the accumulation LC3A/B in the presence of chloroquine, implying that telmisartan acts after the autophagosome-lysosome fusion step. To assess the effects of telmisartan in vivo, we used an orthotopic PDAC model. Telmisartan monotherapy inhibited the growth of primary tumors, decreased the incidence of liver metastasis, and significantly improved the survival of mice. Hence, telmisartan can reduce autophagy and the viability of PDAC cells, and PDAC progression. Because telmisartan is an FDA-approved drug, our findings provide the scientific rationale for testing its efficacy in the prevention of PDAC progression. Citation Format: Jelena Grahovac, Shiwei Han, Hao Liu, Mark Duquette, Alba Luengo, Daniel Schanne, Andrew S. Liss, Matthew G. Vander Heiden, Rakesh K. Jain, Yves Boucher. The angiotensin receptor blocker and partial PPARγ agonist telmisartan inhibits the growth of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.PANCA19-B06
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    detail.hit.zdb_id: 410466-3
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  • 9
    Online Resource
    Online Resource
    Abstract NG10: A metastasis map of human cancer cell lines
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. NG10-NG10
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. NG10-NG10
    Abstract: Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical due to the inherent scale limitation of the in vivo models. Here we introduce an in vivo barcoding strategy capable of determining the metastatic potential of human cancer cell lines in murine xenografts at scale. We validated the robustness, scalability and reproducibility of the method, and applied it to 500 cell lines spanning 21 solid cancer types. We created a first-generation Metastasis Map (MetMap) that reveals organ-specific patterns of metastasis and allows relating those patterns to clinical and genomic features. We demonstrated the utility of MetMap by exploring the molecular basis of breast cancers capable of metastasizing to the brain - a principal cause of death in these patients. Breast cancers that were brain metastatic had unexpected genetic, expression, and metabolic evidence of altered lipid metabolism. Perturbing lipid metabolism curbed brain metastasis development and limited the outgrowth of cancer cells in the brain, suggesting a therapeutic strategy to combat the disease. These results illustrated the utility of MetMap as a step towards next-generation approach for high-throughput metastasis research. Citation Format: Xin Jin, Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Vander Heiden, Todd R. Golub. A metastasis map of human cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr NG10.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-NG10
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 10
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    Abstract A018: Increased RAD21 promotes prostate cancer development
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 11_Supplement ( 2023-06-02), p. A018-A018
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 11_Supplement ( 2023-06-02), p. A018-A018
    Abstract: Prostate cancer (PCa) is one of the most common cancers among men, leading to the second cause of death for men with cancers in the US. Aneuploidy, featured by imbalanced chromosome numbers, is a hallmark of cancer. Epidemiology studies on primary PCa cohorts of Physicians' Health Study and Health Professionals Follow-up Study (PHS and HPFS) have shown that high levels of whole-genome aneuploidy correlate with lethal progression in PCa. However, the detail mechanisms of how aneuploidy drives aggressiveness of PCa are still unclear. Here, we used the case of chromosome 8q (chr 8q, the long arm of chr 8) gain to study aneuploidy-associated prostatic malignancies. Chr 8q gains are the most frequently gain events that occur in around 23% of PCa cases. By using the PHS and HPFS cohorts, we modeled the increased expression of each gene located on chr 8q, for predicting the risks for lethal progression, and obtained the odds ratio (OR) for each. Then, we ranked the ORs for lethal progression and identified several important genes highly associated with lethality when overexpressed. Among them, the cohesin subunit gene, RAD21, is one of the top associators. Increased RAD21 mRNA level, per se, is highly correlated with lethality in all PCa cases, and the lethality is synergistically aggravated in the cases with both increased RAD21 expression and chr 8q gains. indicating that RAD21 cooperates with other chr 8q genes to drive cancer progression and chr 8q gains. To determine how RAD21 overexpression promotes PCa, we studied the effect of overexpression of RAD21 in early prostatic oncogenic events. We utilized the isogenic mouse prostate organoid models carrying an inducible the fusion-oncogene, TMPRSS2-ERG (T-ERG), which 50% of PCa cases harbor. We found that induction of T-ERG leads to a strong oncogenic replication stress at an early stage. Such stress results in an increase in apoptosis and growth impairment in these primary organoids. Overexpression of RAD21, mimicking the chr 8q gain situation, mitigates such replication stress and rescues the growth defect caused by T-ERG. These data suggest the role of increased RAD21 in promoting oncogenic growth of PCa cells by reducing oncogenic toxicity at an early stage. In addition, we showed that such role of RAD21 overexpression sustains in the more advanced cancerous organoid (ERG positive and PTEN loss) and promotes the growth of the cancer organoids. Consistently, increased RAD21 expression correlates with increase proliferative markers in human prostate cancer cases. In conclusion, we identified that overexpression of multiple chr 8q genes are correlated with lethal progression in primary PCa, and RAD21 is one of such genes. Increased RAD21 plays a fundamental role in reducing toxic DNA damage caused by prostatic oncogenesis. Citation Format: Xiaofeng A. Su, Konrad H. Stopsack, Daniel R. Schmidt, Duanduan Ma, Zhe Li, Matthew G. Vander Heiden, Angelika Amon, Lorelei A. Mucci. Increased RAD21 promotes prostate cancer development [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A018.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.PRCA2023-A018
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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