Ubiquitination in cancer stem cell: roles and targeted cancer therapy

  • Liu Liu Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
  • Shasha Yin Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
  • Charles Brobbey Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
  • Wenjian Gan Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
Keywords: Cancer stem cell, Ubiquitination, E3 ligase, Cell signaling, Transcription factor

Abstract

Cancer stem cells (CSCs) are a small subset of stem-like cells inside tumors, which possess abilities of unlimited self-renewal, differentiation and proliferation. Extensive studies have suggested that CSCs are one of the major drivers of tumor initiation, metastasis, relapse and therapeutic resistance. Several regulatory networks including transcriptional programs and various signaling pathways tightly control the stemness, proliferation and differentiation of CSCs. Emerging evidence has indicated that post-translational modifications, especially ubiquitination, play a critical role in maintenance of CSC properties. In this review, we summarize current understandings on E3 ubiquitin ligase-mediated regulation of transcription factors and key signaling pathways involved in the regulation of CSCs, and discuss the strategy to target CSCs and E3 ubiquitin ligases for combating cancers.

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Author Biography

Liu Liu, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA

Department of Biochemistry & Molecular Biology, Postdoc.

References

Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013;108(3):479-85.

Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010;1805(1):105-17.

Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14(3):275-91.

Capp JP. Cancer stem cells: from historical roots to a new perspective. J Oncol. 2019;2019:5189232.

Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730-7.

Bighetti-Trevisan RL, Sousa LO, Castilho RM, Almeida LO. Cancer stem cells: powerful targets to improve current anticancer therapeutics. Stem Cells Int. 2019;2019:9618065.

Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(1):20.

Phi LTH, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, et al. Cancer stem cells (CSCs) in drug eesistance and their therapeutic implications in cancer treatment. Stem Cells Int. 2018;2018:5416923.

Batlle E, Clevers H. Cancer stem cells revisited. Nat Med. 2017;23(10):1124-34.

Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16(3):225-38.

Shetzer Y, Molchadsky A, Rotter V. Oncogenic mutant p53 gain of function nourishes the vicious cycle of tumor development and cancer stem-cell formation. Cold Spring Harb Perspect Med. 2016;6(10).

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76.

Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003;113(5):643-55.

Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113(5):631-42.

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917-20.

Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, et al. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature. 2011;474(7350):225-9.

Suva ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell. 2014;157(3):580-94.

Matsui WH. Cancer stem cell signaling pathways. Medicine (Baltimore). 2016;95(1 Suppl 1):S8-S19.

Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104(41):16158-63.

Sherry MM, Reeves A, Wu JK, Cochran BH. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells. 2009;27(10):2383-92.

Yin X, Zhang BH, Zheng SS, Gao DM, Qiu SJ, Wu WZ, et al. Coexpression of gene Oct4 and Nanog initiates stem cell characteristics in hepatocellular carcinoma and promotes epithelial-mesenchymal transition through activation of Stat3/Snail signaling. J Hematol Oncol. 2015;8:23.

Do DV, Ueda J, Messerschmidt DM, Lorthongpanich C, Zhou Y, Feng B, et al. A genetic and developmental pathway from STAT3 to the OCT4-NANOG circuit is essential for maintenance of ICM lineages in vivo. Genes Dev. 2013;27(12):1378-90.

Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425-79.

Skaar JR, Pagan JK, Pagano M. SCF ubiquitin ligase-targeted therapies. Nat Rev Drug Discov. 2014;13(12):889-903.

Zheng N, Shabek N. Ubiquitin Ligases: Structure, Function, and Regulation. Annu Rev Biochem. 2017;86:129-57.

Wang D, Ma L, Wang B, Liu J, Wei W. E3 ubiquitin ligases in cancer and implications for therapies. Cancer Metastasis Rev. 2017;36(4):683-702.

Akutsu M, Dikic I, Bremm A. Ubiquitin chain diversity at a glance. J Cell Sci. 2016;129(5):875-80.

Kang B, Sun XH. Regulation of cancer stem cells by RING finger ubiquitin ligases. Stem Cell Investig. 2014;1:5.

Amm I, Sommer T, Wolf DH. Protein quality control and elimination of protein waste: the role of the ubiquitin-proteasome system. Biochim Biophys Acta. 2014;1843(1):182-96.

Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000;24(4):372-6.

Kim RJ, Nam JS. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab Anim Res. 2011;27(2):147-52.

Chang CC, Shieh GS, Wu P, Lin CC, Shiau AL, Wu CL. Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res. 2008;68(15):6281-91.

Xu H, Wang W, Li C, Yu H, Yang A, Wang B, et al. WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 2009;19(5):561-73.

Liao B, Zhong X, Xu H, Xiao F, Fang Z, Gu J, et al. Itch, an E3 ligase of Oct4, is required for embryonic stem cell self-renewal and pluripotency induction. J Cell Physiol. 2013;228(7):1443-51.

Cho Y, Kang HG, Kim SJ, Lee S, Jee S, Ahn SG, et al. Post-translational modification of OCT4 in breast cancer tumorigenesis. Cell Death Differ. 2018;25(10):1781-95.

Mamun MA, Mannoor K, Cao J, Qadri F, Song X. SOX2 in cancer stemness: tumor malignancy and therapeutic potentials. J Mol Cell Biol. 2020;12(2):85-98.

Fang L, Zhang L, Wei W, Jin X, Wang P, Tong Y, et al. A methylation-phosphorylation switch determines Sox2 stability and function in ESC maintenance or differentiation. Mol Cell. 2014;55(4):537-51.

Wang J, Zhang Y, Hou J, Qian X, Zhang H, Zhang Z, et al. Ube2s regulates Sox2 stability and mouse ES cell maintenance. Cell Death Differ. 2016;23(3):393-404.

Cui CP, Zhang Y, Wang C, Yuan F, Li H, Yao Y, et al. Dynamic ubiquitylation of Sox2 regulates proteostasis and governs neural progenitor cell differentiation. Nat Commun. 2018;9(1):4648.

Wang L, Shen F, Stroehlein JR, Wei D. Context-dependent functions of KLF4 in cancers: could alternative splicing isoforms be the key? Cancer Lett. 2018;438:10-6.

Yu F, Li J, Chen H, Fu J, Ray S, Huang S, et al. Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene. 2011;30(18):2161-72.

Zhou H, Liu Y, Zhu R, Ding F, Wan Y, Li Y, et al. FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation. Oncogene. 2017;36(23):3312-21.

Hao Z, Sheng Y, Duncan GS, Li WY, Dominguez C, Sylvester J, et al. K48-linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression. Nat Commun. 2017;8:14003.

He H, Wu Z, Li S, Chen K, Wang D, Zou H, et al. TRAF7 enhances ubiquitin-degradation of KLF4 to promote hepatocellular carcinoma progression. Cancer Lett. 2020;469:380-9.

Chen H, Liu H, Qing G. Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018;3:5.

Yang A, Qin S, Schulte BA, Ethier SP, Tew KD, Wang GY. MYC Inhibition Depletes Cancer Stem-like Cells in Triple-Negative Breast Cancer. Cancer Res. 2017;77(23):6641-50.

Gregory MA, Hann SR. c-Myc proteolysis by the ubiquitin-proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells. Mol Cell Biol. 2000;20(7):2423-35.

King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, et al. The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell. 2013;153(7):1552-66.

Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM, et al. Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med. 2008;205(6):1395-408.

Reavie L, Della Gatta G, Crusio K, Aranda-Orgilles B, Buckley SM, Thompson B, et al. Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nat Immunol. 2010;11(3):207-15.

Takeishi S, Matsumoto A, Onoyama I, Naka K, Hirao A, Nakayama KI. Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence. Cancer Cell. 2013;23(3):347-61.

Popov N, Schulein C, Jaenicke LA, Eilers M. Ubiquitylation of the amino terminus of Myc by SCF(beta-TrCP) antagonizes SCF(Fbw7)-mediated turnover. Nat Cell Biol. 2010;12(10):973-81.

Adhikary S, Marinoni F, Hock A, Hulleman E, Popov N, Beier R, et al. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell. 2005;123(3):409-21.

Kim EJ, Kim SH, Jin X, Jin X, Kim H. KCTD2, an adaptor of Cullin3 E3 ubiquitin ligase, suppresses gliomagenesis by destabilizing c-Myc. Cell Death Differ. 2017;24(4):649-59.

Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, et al. Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther. 2010;9(4):295-302.

Wang ML, Chiou SH, Wu CW. Targeting cancer stem cells: emerging role of Nanog transcription factor. Onco Targets Ther. 2013;6:1207-20.

Zhang J, Chen M, Zhu Y, Dai X, Dang F, Ren J, et al. SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression. Dev Cell. 2019;48(3):329-44 e5.

Kim SH, Kim MO, Cho YY, Yao K, Kim DJ, Jeong CH, et al. ERK1 phosphorylates Nanog to regulate protein stability and stem cell self-renewal. Stem Cell Res. 2014;13(1):1-11.

Balzeau J, Menezes MR, Cao S, Hagan JP. The LIN28/let-7 Pathway in Cancer. Front Genet. 2017;8:31.

Zhou J, Ng SB, Chng WJ. LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells. Int J Biochem Cell Biol. 2013;45(5):973-8.

Lee SH, Cho S, Kim MS, Choi K, Cho JY, Gwak HS, et al. The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein. Biochim Biophys Acta. 2014;1839(5):374-86.

Karve TM, Cheema AK. Small changes huge impact: the role of protein posttranslational modifications in cellular homeostasis and disease. J Amino Acids. 2011;2011:207691.

Guruharsha KG, Kankel MW, Artavanis-Tsakonas S. The Notch signalling system: recent insights into the complexity of a conserved pathway. Nat Rev Genet. 2012;13(9):654-66.

Fryer CJ, White JB, Jones KA. Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell. 2004;16(4):509-20.

Haydu JE, De Keersmaecker K, Duff MK, Paietta E, Racevskis J, Wiernik PH, et al. An activating intragenic deletion in NOTCH1 in human T-ALL. Blood. 2012;119(22):5211-4.

Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI. Fbxw7-dependent degradation of Notch is required for control of "stemness" and neuronal-glial differentiation in neural stem cells. J Biol Chem. 2011;286(15):13754-64.

Qiu L, Joazeiro C, Fang N, Wang HY, Elly C, Altman Y, et al. Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase. J Biol Chem. 2000;275(46):35734-7.

Weinmaster G, Fischer JA. Notch ligand ubiquitylation: what is it good for? Dev Cell. 2011;21(1):134-44.

de Sousa EMF, Vermeulen L. Wnt signaling in cancer stem cell biology. Cancers (Basel). 2016;8(7).

Komiya Y, Habas R. Wnt signal transduction pathways. Organogenesis. 2008;4(2):68-75.

Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485(7397):195-200.

Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488(7413):665-9.

Funato Y, Terabayashi T, Sakamoto R, Okuzaki D, Ichise H, Nojima H, et al. Nucleoredoxin sustains Wnt/beta-catenin signaling by retaining a pool of inactive dishevelled protein. Curr Biol. 2010;20(21):1945-52.

Wei W, Li M, Wang J, Nie F, Li L. The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled protein. Mol Cell Biol. 2012;32(19):3903-12.

Ding Y, Zhang Y, Xu C, Tao QH, Chen YG. HECT domain-containing E3 ubiquitin ligase NEDD4L negatively regulates Wnt signaling by targeting dishevelled for proteasomal degradation. J Biol Chem. 2013;288(12):8289-98.

Liu C, Kato Y, Zhang Z, Do VM, Yankner BA, He X. beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci U S A. 1999;96(11):6273-8.

Zhang Y, Liu S, Mickanin C, Feng Y, Charlat O, Michaud GA, et al. RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nat Cell Biol. 2011;13(5):623-9.

Fei C, He X, Xie S, Miao H, Zhou Z, Li L. Smurf1-mediated axin ubiquitination requires Smurf1 C2 domain and is cell cycle-dependent. J Biol Chem. 2014;289(20):14170-7.

Ji L, Jiang B, Jiang X, Charlat O, Chen A, Mickanin C, et al. The SIAH E3 ubiquitin ligases promote Wnt/beta-catenin signaling through mediating Wnt-induced Axin degradation. Genes Dev. 2017;31(9):904-15.

Lee HK, Lee EW, Seo J, Jeong M, Lee SH, Kim SY, et al. Ubiquitylation and degradation of adenomatous polyposis coli by MKRN1 enhances Wnt/beta-catenin signaling. Oncogene. 2018;37(31):4273-86.

Tauriello DV, Maurice MM. The various roles of ubiquitin in Wnt pathway regulation. Cell Cycle. 2010;9(18):3700-9.

Wicking C, McGlinn E. The role of hedgehog signalling in tumorigenesis. Cancer Lett. 2001;173(1):1-7.

Cochrane CR, Szczepny A, Watkins DN, Cain JE. Hedgehog Signaling in the Maintenance of Cancer Stem Cells. Cancers (Basel). 2015;7(3):1554-85.

Yue S, Tang LY, Tang Y, Tang Y, Shen QH, Ding J, et al. Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception. Elife. 2014;3.

Chen XL, Chinchilla P, Fombonne J, Ho L, Guix C, Keen JH, et al. Patched-1 proapoptotic activity is downregulated by modification of K1413 by the E3 ubiquitin-protein ligase Itchy homolog. Mol Cell Biol. 2014;34(20):3855-66.

Xia R, Jia H, Fan J, Liu Y, Jia J. USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization. PLoS Biol. 2012;10(1):e1001238.

Li S, Chen Y, Shi Q, Yue T, Wang B, Jiang J. Hedgehog-regulated ubiquitination controls smoothened trafficking and cell surface expression in Drosophila. PLoS Biol. 2012;10(1):e1001239.

Raducu M, Fung E, Serres S, Infante P, Barberis A, Fischer R, et al. SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development. EMBO J. 2016;35(13):1400-16.

Infante P, Faedda R, Bernardi F, Bufalieri F, Lospinoso Severini L, Alfonsi R, et al. Itch/beta-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis. Nat Commun. 2018;9(1):976.

Bhatia N, Thiyagarajan S, Elcheva I, Saleem M, Dlugosz A, Mukhtar H, et al. Gli2 is targeted for ubiquitination and degradation by beta-TrCP ubiquitin ligase. J Biol Chem. 2006;281(28):19320-6.

Wang B, Li Y. Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Proc Natl Acad Sci U S A. 2006;103(1):33-8.

Zhang Q, Shi Q, Chen Y, Yue T, Li S, Wang B, et al. Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase. Proc Natl Acad Sci U S A. 2009;106(50):21191-6.

Deng W, Vanderbilt DB, Lin CC, Martin KH, Brundage KM, Ruppert JM. SOX9 inhibits beta-TrCP-mediated protein degradation to promote nuclear GLI1 expression and cancer stem cell properties. J Cell Sci. 2015;128(6):1123-38.

Hatakeyama S. Ubiquitin-mediated regulation of JAK-STAT signaling in embryonic stem cells. JAKSTAT. 2012;1(3):168-75.

Yang WL, Wu CY, Wu J, Lin HK. Regulation of Akt signaling activation by ubiquitination. Cell Cycle. 2010;9(3):487-97.

Chen ZJ. Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol. 2005;7(8):758-65.

Shih Ie M, Wang TL. Notch signaling, gamma-secretase inhibitors, and cancer therapy. Cancer Res. 2007;67(5):1879-82.

Capodanno Y, Buishand FO, Pang LY, Kirpensteijn J, Mol JA, Argyle DJ. Notch pathway inhibition targets chemoresistant insulinoma cancer stem cells. Endocr Relat Cancer. 2018;25(2):131-44.

Proctor AE, Thompson LA, O'Bryant CL. Vismodegib: an inhibitor of the Hedgehog signaling pathway in the treatment of basal cell carcinoma. Ann Pharmacother. 2014;48(1):99-106.

Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018;62:50-60.

Darnell JE, Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer. 2002;2(10):740-9.

Toh TB, Lim JJ, Chow EK. Epigenetics in cancer stem cells. Mol Cancer. 2017;16(1):29.

Xun J, Wang D, Shen L, Gong J, Gao R, Du L, et al. JMJD3 suppresses stem cell-like characteristics in breast cancer cells by downregulation of Oct4 independently of its demethylase activity. Oncotarget. 2017;8(13):21918-29.

Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904-17.

Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011;108(40):16669-74.

Paiva SL, Crews CM. Targeted protein degradation: elements of PROTAC design. Curr Opin Chem Biol. 2019;50:111-9.

Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, et al. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015;348(6241):1376-81.

Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, et al. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015;22(6):755-63.

Huang HL, Weng HY, Wang LQ, Yu CH, Huang QJ, Zhao PP, et al. Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis. Mol Cancer Ther. 2012;11(5):1155-65.

Jung J, Kim Y, Song J, Yoon YJ, Kim DE, Kim JA, et al. KRIBB53 binds to OCT4 and enhances its degradation through the proteasome, causing apoptotic cell death of OCT4-positive testicular germ cell tumors. Carcinogenesis. 2018;39(6):838-49.

Han H, Jain AD, Truica MI, Izquierdo-Ferrer J, Anker JF, Lysy B, et al. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell. 2019;36(5):483-97 e15.

Huang MJ, Cheng YC, Liu CR, Lin S, Liu HE. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol. 2006;34(11):1480-9.

Matkar S, Sharma P, Gao S, Gurung B, Katona BW, Liao J, et al. An epigenetic pathway regulates sensitivity of breast cancer cells to HER2 inhibition via FOXO/c-Myc axis. Cancer Cell. 2015;28(4):472-85.

Roos M, Pradere U, Ngondo RP, Behera A, Allegrini S, Civenni G, et al. A small-molecule inhibitor of Lin28. ACS Chem Biol. 2016;11(10):2773-81.

Massard C, Azaro A, Soria JC, Lassen U, Le Tourneau C, Sarker D, et al. First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer. Ann Oncol. 2018;29(9):1911-7.

Cook N, Basu B, Smith DM, Gopinathan A, Evans J, Steward WP, et al. A phase I trial of the gamma-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma. Br J Cancer. 2018;118(6):793-801.

A phase I study of AL101, a pan-NOTCH inhibitor, in patients (pts) with locally advanced or metastatic solid tumors J Clin Oncol. 2018;36:15_suppl,2515.

ACCURACY: phase (P) 2 trial of AL101, a pan-Notch inhibitor, in patients (pts) with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) with Notch activating mutations (Notchact mut). J Clin Oncol. 2019;37:15_suppl,TPS6098.

Smith DC, Rosen LS, Chugh R, et al. First-in-human evaluation of the human monoclonal antibody vantictumab (OMP-18r5; anti-Frizzled) targeting the WNT pathway in a phase I study for patients with advanced solid tumors. J Clin Oncol. 2013;31:15_suppl,2540.

Shan J, Shi DL, Wang J, Zheng J. Identification of a specific inhibitor of the dishevelled PDZ domain. Biochemistry. 2005;44(47):15495-503.

Kimura K, Ikoma A, Shibakawa M, Shimoda S, Harada K, Saio M, et al. Safety, tolerability, and preliminary efficacy of the anti-fibrotic small molecule PRI-724, a CBP/beta-catenin inhibitor, in patients with hepatitis C virus-related virrhosis: a single-center, open-label, dose escalation phase 1 trial. EBioMedicine. 2017;23:79-87.

A study of E-7386 in participants with advanced solid tumor including colorectal cancer (CRC) (NCT03833700, 2019). Available online at: https://clinicaltrials.gov/ct2/show/NCT03833700

Phase I, open-label, non-randomized study to evaluate safety of BC2059 (NCT03459469, 2018). Available online at: https://clinicaltrials.gov/ct2/show/NCT03459469

Lu J, Ma Z, Hsieh JC, Fan CW, Chen B, Longgood JC, et al. Structure-activity relationship studies of small-molecule inhibitors of Wnt response. Bioorg Med Chem Lett. 2009;19(14):3825-7.

Axelson M, Liu K, Jiang X, He K, Wang J, Zhao H, et al. U.S. Food and drug administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Clin Cancer Res. 2013;19(9):2289-93.

Study of patidegib topical gel, 2%, for the reduction of disease burden of persistently developing basal cell carcinomas (BCCs) in subjects with basal cell nevus syndrome (Gorlin Syndrome) (NCT03703310, 2018). Available online at: https://clinicaltrials.gov/ct2/show/NCT03703310

Taladegib, paclitaxel, carboplatin, and radiation therapy in treating patients with localized esophageal or gastroesophageal junction cancer (NCT02530437, 2015). Available online at: https://clinicaltrials.gov/ct2/show/NCT02530437

Published
2020-03-30
How to Cite
Liu, L., Yin, S., Brobbey, C., & Gan, W. (2020). Ubiquitination in cancer stem cell: roles and targeted cancer therapy. STEMedicine, 1(3), e37. https://doi.org/10.37175/stemedicine.v1i3.37
Section
Review articles