{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:55:56Z","timestamp":1794009356479,"version":"4.8.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Materials and methods<\/jats:title>\n                <jats:p>Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6\u2009~\u20098\u2009weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Result<\/jats:title>\n                <jats:p>Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2, 3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-\u03baB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp\/TDO2\/Kyn\/AhR\/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR\/c-Myc\/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism\/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12885-021-08855-9","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T08:06:20Z","timestamp":1634457980000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tryptophan metabolism induced by TDO2 promotes prostatic cancer chemotherapy resistance in a AhR\/c-Myc dependent manner"],"prefix":"10.1186","volume":"21","author":[{"given":"Fan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongbiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"issue":"1","key":"8855_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21551","volume":"69","author":"RL Siegel","year":"2019","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7\u201334. https:\/\/doi.org\/10.3322\/caac.21551.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"8855_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21442","volume":"68","author":"RL Siegel","year":"2018","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7\u201330. https:\/\/doi.org\/10.3322\/caac.21442.","journal-title":"CA Cancer J Clin"},{"issue":"3","key":"8855_CR3","doi-asserted-by":"publisher","first-page":"157","DOI":"10.4111\/kju.2011.52.3.157","volume":"52","author":"SJ Kim","year":"2011","unstructured":"Kim SJ, Kim SI. Current treatment strategies for castration-resistant prostate cancer. Korean J Urol. 2011;52(3):157\u201365. https:\/\/doi.org\/10.4111\/kju.2011.52.3.157.","journal-title":"Korean J Urol"},{"issue":"2","key":"8855_CR4","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1159\/000071510","volume":"26","author":"JP van Brussel","year":"2003","unstructured":"van Brussel JP, Mickisch GH. Multidrug resistance in prostate cancer. Onkologie. 2003;26(2):175\u201381. https:\/\/doi.org\/10.1159\/000071510.","journal-title":"Onkologie"},{"issue":"10","key":"8855_CR5","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s11912-015-0468-7","volume":"17","author":"M Hurwitz","year":"2015","unstructured":"Hurwitz M. Chemotherapy in prostate Cancer. Curr Oncol Rep. 2015;17(10):44. https:\/\/doi.org\/10.1007\/s11912-015-0468-7.","journal-title":"Curr Oncol Rep"},{"key":"8855_CR6","doi-asserted-by":"publisher","unstructured":"Costea T, Vlad OC, Miclea LC, Ganea C, Sz\u00f6ll\u0151si J, Mocanu MM: Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer. Int J Mol Sci 2020, 21(2), 21, 2, doi: https:\/\/doi.org\/10.3390\/ijms21020401.","DOI":"10.3390\/ijms21020401"},{"issue":"4","key":"8855_CR7","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","volume":"168","author":"MG Vander Heiden","year":"2017","unstructured":"Vander Heiden MG, DeBerardinis RJ. Understanding the intersections between metabolism and Cancer biology. Cell. 2017;168(4):657\u201369. https:\/\/doi.org\/10.1016\/j.cell.2016.12.039.","journal-title":"Cell"},{"issue":"5","key":"8855_CR8","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41573-019-0016-5","volume":"18","author":"M Platten","year":"2019","unstructured":"Platten M, Nollen EAA, R\u00f6hrig UF, Fallarino F, Opitz CA. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019;18(5):379\u2013401. https:\/\/doi.org\/10.1038\/s41573-019-0016-5.","journal-title":"Nat Rev Drug Discov"},{"issue":"4","key":"8855_CR9","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/bju.15205","volume":"127","author":"SH Lee","year":"2020","unstructured":"Lee SH, Mahendran R, Tham SM, Thamboo TP, Chionh BJ, Lim YX, et al. Tryptophan-kynurenine ratio as a biomarker of bladder cancer. BJU Int. 2020;127(4):445\u201353. https:\/\/doi.org\/10.1111\/bju.15205.","journal-title":"BJU Int"},{"issue":"21","key":"8855_CR10","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1158\/0008-5472.CAN-15-2011","volume":"75","author":"NC D'Amato","year":"2015","unstructured":"D'Amato NC, Rogers TJ, Gordon MA, Greene LI, Cochrane DR, Spoelstra NS, et al. A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer. Cancer Res. 2015;75(21):4651\u201364. https:\/\/doi.org\/10.1158\/0008-5472.CAN-15-2011.","journal-title":"Cancer Res"},{"issue":"17\u201318","key":"8855_CR11","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1101\/gad.327056.119","volume":"33","author":"N Venkateswaran","year":"2019","unstructured":"Venkateswaran N, Lafita-Navarro MC, Hao YH, Kilgore JA, Perez-Castro L, Braverman J, et al. MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer. Genes Dev. 2019;33(17\u201318):1236\u201351. https:\/\/doi.org\/10.1101\/gad.327056.119.","journal-title":"Genes Dev"},{"key":"8855_CR12","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.ijid.2019.12.005","volume":"91","author":"S Geisler","year":"2020","unstructured":"Geisler S, Lytton SD, Toan NL, Nghia TH, Nam NM, Hung HV, et al. Neopterin levels and Kyn\/Trp ratios were significantly increased in dengue virus patients and subsequently decreased after recovery. Int J Infect Dis. 2020;91:162\u20138. https:\/\/doi.org\/10.1016\/j.ijid.2019.12.005.","journal-title":"Int J Infect Dis"},{"issue":"1","key":"8855_CR13","doi-asserted-by":"publisher","first-page":"1777625","DOI":"10.1080\/2162402X.2020.1777625","volume":"9","author":"J Le Naour","year":"2020","unstructured":"Le Naour J, Galluzzi L, Zitvogel L, Kroemer G, Vacchelli E. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology. 2020;9(1):1777625. https:\/\/doi.org\/10.1080\/2162402X.2020.1777625.","journal-title":"Oncoimmunology"},{"issue":"1","key":"8855_CR14","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1756-6606-2-8","volume":"2","author":"M Kanai","year":"2009","unstructured":"Kanai M, Funakoshi H, Takahashi H, Hayakawa T, Mizuno S, Matsumoto K, et al. Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice. Mol Brain. 2009;2(1):8. https:\/\/doi.org\/10.1186\/1756-6606-2-8.","journal-title":"Mol Brain"},{"key":"8855_CR15","doi-asserted-by":"publisher","first-page":"673","DOI":"10.3389\/fimmu.2014.00673","volume":"5","author":"M Platten","year":"2014","unstructured":"Platten M, von Knebel DN, Oezen I, Wick W, Ochs K. Cancer immunotherapy by targeting IDO1\/TDO and their downstream effectors. Front Immunol. 2014;5:673. https:\/\/doi.org\/10.3389\/fimmu.2014.00673.","journal-title":"Front Immunol"},{"issue":"12","key":"8855_CR16","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.7150\/jca.31727","volume":"10","author":"Z Ye","year":"2019","unstructured":"Ye Z, Yue L, Shi J, Shao M, Wu T. Role of IDO and TDO in cancers and related diseases and the therapeutic implications. J Cancer. 2019;10(12):2771\u201382. https:\/\/doi.org\/10.7150\/jca.31727.","journal-title":"J Cancer"},{"issue":"11","key":"8855_CR17","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1096\/fasebj.5.11.1907934","volume":"5","author":"MW Taylor","year":"1991","unstructured":"Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991;5(11):2516\u201322. https:\/\/doi.org\/10.1096\/fasebj.5.11.1907934.","journal-title":"FASEB J"},{"issue":"10","key":"8855_CR18","doi-asserted-by":"publisher","first-page":"6303","DOI":"10.4049\/jimmunol.0901577","volume":"183","author":"F Fallarino","year":"2009","unstructured":"Fallarino F, Volpi C, Zelante T, Vacca C, Calvitti M, Fioretti MC, et al. IDO mediates TLR9-driven protection from experimental autoimmune diabetes. J Immunol. 2009;183(10):6303\u201312. https:\/\/doi.org\/10.4049\/jimmunol.0901577.","journal-title":"J Immunol"},{"issue":"9","key":"8855_CR19","doi-asserted-by":"publisher","first-page":"5601","DOI":"10.4049\/jimmunol.175.9.5601","volume":"175","author":"AL Mellor","year":"2005","unstructured":"Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN type 1 signaling. J Immunol. 2005;175(9):5601\u20135. https:\/\/doi.org\/10.4049\/jimmunol.175.9.5601.","journal-title":"J Immunol"},{"issue":"9","key":"8855_CR20","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1158\/2326-6066.CIR-14-0167","volume":"3","author":"A Holtzhausen","year":"2015","unstructured":"Holtzhausen A, Zhao F, Evans KS, Tsutsui M, Orabona C, Tyler DS, et al. Melanoma-derived Wnt5a promotes local dendritic-cell expression of IDO and Immunotolerance: opportunities for pharmacologic enhancement of immunotherapy. Cancer Immunol Res. 2015;3(9):1082\u201395. https:\/\/doi.org\/10.1158\/2326-6066.CIR-14-0167.","journal-title":"Cancer Immunol Res"},{"issue":"4","key":"8855_CR21","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.18632\/oncotarget.1637","volume":"5","author":"UM Litzenburger","year":"2014","unstructured":"Litzenburger UM, Opitz CA, Sahm F, Rauschenbach KJ, Trump S, Winter M, et al. Constitutive IDO expression in human cancer is sustained by an autocrine signaling loop involving IL-6, STAT3 and the AHR. Oncotarget. 2014;5(4):1038\u201351. https:\/\/doi.org\/10.18632\/oncotarget.1637.","journal-title":"Oncotarget"},{"issue":"1","key":"8855_CR22","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.gene.2007.04.010","volume":"396","author":"HJ Ball","year":"2007","unstructured":"Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene. 2007;396(1):203\u201313. https:\/\/doi.org\/10.1016\/j.gene.2007.04.010.","journal-title":"Gene"},{"issue":"15","key":"8855_CR23","doi-asserted-by":"publisher","first-page":"7082","DOI":"10.1158\/0008-5472.CAN-07-1872","volume":"67","author":"R Metz","year":"2007","unstructured":"Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. 2007;67(15):7082\u20137. https:\/\/doi.org\/10.1158\/0008-5472.CAN-07-1872.","journal-title":"Cancer Res"},{"issue":"5380","key":"8855_CR24","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1126\/science.281.5380.1191","volume":"281","author":"DH Munn","year":"1998","unstructured":"Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science. 1998;281(5380):1191\u20133. https:\/\/doi.org\/10.1126\/science.281.5380.1191.","journal-title":"Science"},{"issue":"3","key":"8855_CR25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.tips.2017.11.007","volume":"39","author":"JE Cheong","year":"2018","unstructured":"Cheong JE, Sun L. Targeting the IDO1\/TDO2-KYN-AhR pathway for Cancer immunotherapy - challenges and opportunities. Trends Pharmacol Sci. 2018;39(3):307\u201325. https:\/\/doi.org\/10.1016\/j.tips.2017.11.007.","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"8855_CR26","doi-asserted-by":"publisher","first-page":"22","DOI":"10.23736\/S0393-2249.17.02976-9","volume":"70","author":"C DEN","year":"2018","unstructured":"DEN C, Presicce F, Giacinti S, Bassanelli M. Tubaro a: castration-resistance prostate cancer: what is in the pipeline? Minerva Urol Nefrol. 2018;70(1):22\u201341. https:\/\/doi.org\/10.23736\/S0393-2249.17.02976-9.","journal-title":"Minerva Urol Nefrol"},{"issue":"7","key":"8855_CR27","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1056\/NEJMra1701695","volume":"378","author":"O Sartor","year":"2018","unstructured":"Sartor O, de Bono JS. Metastatic prostate Cancer. N Engl J Med. 2018;378(7):645\u201357. https:\/\/doi.org\/10.1056\/NEJMra1701695.","journal-title":"N Engl J Med"},{"issue":"10","key":"8855_CR28","doi-asserted-by":"publisher","first-page":"5231","DOI":"10.21873\/anticanres.13720","volume":"39","author":"K Mokbel","year":"2019","unstructured":"Mokbel K, Wazir U, Mokbel K. Chemoprevention of prostate Cancer by natural agents: evidence from molecular and epidemiological studies. Anticancer Res. 2019;39(10):5231\u201359. https:\/\/doi.org\/10.21873\/anticanres.13720.","journal-title":"Anticancer Res"},{"key":"8855_CR29","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fcimb.2018.00013","volume":"8","author":"J Gao","year":"2018","unstructured":"Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, et al. Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol. 2018;8:13. https:\/\/doi.org\/10.3389\/fcimb.2018.00013.","journal-title":"Front Cell Infect Microbiol"},{"key":"8855_CR30","doi-asserted-by":"publisher","unstructured":"Schenk A, Esser T, Knoop A, Thevis M, Herden J, Heidenreich A, Bloch W, Joisten N, Zimmer P: Effect of a Single Bout of Aerobic Exercise on Kynurenine Pathway Metabolites and Inflammatory Markers in Prostate Cancer Patients-A Pilot Randomized Controlled Trial. Metabolites 2020, 11(1), Effect of a Single Bout of Aerobic Exercise on Kynurenine Pathway Metabolites and Inflammatory Markers in Prostate Cancer Patients\u2014A Pilot Randomized Controlled Trial, 11, 1, doi: https:\/\/doi.org\/10.3390\/metabo11010004.","DOI":"10.3390\/metabo11010004"},{"key":"8855_CR31","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/bs.ircmb.2017.07.004","volume":"336","author":"GC Prendergast","year":"2018","unstructured":"Prendergast GC, Malachowski WJ, Mondal A, Scherle P, Muller AJ. Indoleamine 2,3-Dioxygenase and its therapeutic inhibition in Cancer. Int Rev Cell Mol Biol. 2018;336:175\u2013203. https:\/\/doi.org\/10.1016\/bs.ircmb.2017.07.004.","journal-title":"Int Rev Cell Mol Biol"},{"key":"8855_CR32","doi-asserted-by":"publisher","first-page":"107746","DOI":"10.1016\/j.pharmthera.2020.107746","volume":"107746","author":"A Dol\u0161ak","year":"2020","unstructured":"Dol\u0161ak A, Gobec S, Sova M. Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets. Pharmacol Ther. 2020;107746:107746. https:\/\/doi.org\/10.1016\/j.pharmthera.2020.107746.","journal-title":"Pharmacol Ther"},{"issue":"7","key":"8855_CR33","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1073\/pnas.1113873109","volume":"109","author":"L Pilotte","year":"2012","unstructured":"Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Fr\u00e9d\u00e9rick R, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2012;109(7):2497\u2013502. https:\/\/doi.org\/10.1073\/pnas.1113873109.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7368","key":"8855_CR34","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature10491","volume":"478","author":"CA Opitz","year":"2011","unstructured":"Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478(7368):197\u2013203. https:\/\/doi.org\/10.1038\/nature10491.","journal-title":"Nature"},{"issue":"7135","key":"8855_CR35","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature05683","volume":"446","author":"F Ohtake","year":"2007","unstructured":"Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, et al. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature. 2007;446(7135):562\u20136. https:\/\/doi.org\/10.1038\/nature05683.","journal-title":"Nature"},{"key":"8855_CR36","doi-asserted-by":"publisher","first-page":"133","DOI":"10.4137\/EHI.S38343","volume":"10","author":"C Jaeger","year":"2016","unstructured":"Jaeger C, Tischkau SA. Role of aryl hydrocarbon receptor in circadian clock disruption and metabolic dysfunction. Environ Health Insights. 2016;10:133\u201341. https:\/\/doi.org\/10.4137\/EHI.S38343.","journal-title":"Environ Health Insights"},{"issue":"9","key":"8855_CR37","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/modpathol.2008.111","volume":"21","author":"B Gurel","year":"2008","unstructured":"Gurel B, Iwata T, Koh CM, Jenkins RB, Lan F, Van Dang C, et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol. 2008;21(9):1156\u201367. https:\/\/doi.org\/10.1038\/modpathol.2008.111.","journal-title":"Mod Pathol"},{"issue":"24","key":"8855_CR38","doi-asserted-by":"publisher","first-page":"6063","DOI":"10.1002\/cncr.27689","volume":"118","author":"ES Antonarakis","year":"2012","unstructured":"Antonarakis ES, Keizman D, Zhang Z, Gurel B, Lotan TL, Hicks JL, et al. An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer. 2012;118(24):6063\u201371. https:\/\/doi.org\/10.1002\/cncr.27689.","journal-title":"Cancer"},{"key":"8855_CR39","doi-asserted-by":"publisher","unstructured":"Zadra G, Loda M: Metabolic Vulnerabilities of Prostate Cancer: Diagnostic and Therapeutic Opportunities. Cold Spring Harb Perspect Med 2018, 8(10), 8, 10, doi: https:\/\/doi.org\/10.1101\/cshperspect.a030569.","DOI":"10.1101\/cshperspect.a030569"},{"key":"8855_CR40","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.semcdb.2015.08.003","volume":"43","author":"AL Hsieh","year":"2015","unstructured":"Hsieh AL, Walton ZE, Altman BJ, Stine ZE, Dang CV. MYC and metabolism on the path to cancer. Semin Cell Dev Biol. 2015;43:11\u201321. https:\/\/doi.org\/10.1016\/j.semcdb.2015.08.003.","journal-title":"Semin Cell Dev Biol"},{"key":"8855_CR41","doi-asserted-by":"publisher","first-page":"117736","DOI":"10.1016\/j.lfs.2020.117736","volume":"253","author":"M Duan","year":"2020","unstructured":"Duan M, Hu F, Li D, Wu S, Peng N. Silencing KPNA2 inhibits IL-6-induced breast cancer exacerbation by blocking NF-\u03baB signaling and c-Myc nuclear translocation in vitro. Life Sci. 2020;253:117736. https:\/\/doi.org\/10.1016\/j.lfs.2020.117736.","journal-title":"Life Sci"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-021-08855-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-021-08855-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-021-08855-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T20:35:24Z","timestamp":1634502924000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-021-08855-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,17]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["8855"],"URL":"https:\/\/doi.org\/10.1186\/s12885-021-08855-9","relation":{},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,17]]},"assertion":[{"value":"20 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethics Committee of the Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology. All samples collection and processing were carried out respecting the Declaration of Helsinki. All patients signed informed consent prior to tumor tissues collection treatment, including allowing their data to be used for further research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1112"}}