Scilight Press

Author Information

Received: 02 May 2024 | Revised: 19 May 2024 | Accepted: 20 May 2024 | Published: 11 Jun 2024

Abstract

Keywords

transcription factor | CREB | tumor development | signaling pathway

References 

• 1.
  Sung, H.; Ferlay, J.; Siegel, R.L.; et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249.
• 2.
  Hoelder, S.; Clarke, P.A.; Workman, P. Discovery of small molecule cancer drugs: Successes, challenges and opportunities. Mol. Oncol. 2012, 6, 155–176.
• 3.
  Hutchinson, L.; Kirk, R. High drug attrition rates--where are we going wrong? Nat. Rev. Clin. Oncol. 2011, 8, 189–190.
• 4.
  Nikolaou, M.; Pavlopoulou, A.; Georgakilas, A.G.; et al. The challenge of drug resistance in cancer treatment: A current overview. Clin. Exp. Metastasis 2018, 35, 309–318.
• 5.
  Toyota, M.; Suzuki, H.; Yamamoto, E.; et al. Integrated analysis of genetic and epigenetic alterations in cancer. Epigenomics 2009, 1, 291–299.
• 6.
  Sieber, O.; Heinimann, K.; Tomlinson, I. Genomic stability and tumorigenesis. Semin Cancer Biol. 2005, 15, 61–66.
• 7.
  Martincorena, I.; Campbell, P.J. Somatic mutation in cancer and normal cells. Science 2015, 349, 1483–1489.
• 8.
  Lambert, S.A.; Jolma, A.; Campitelli, L.F.; et al. The Human Transcription Factors. Cell 2018, 172, 650–665.
• 9.
  Bushweller, J.H. Targeting transcription factors in cancer - from undruggable to reality. Nat. Rev. Cancer 2019, 19, 611–624.
• 10.
  Montminy, M.R.; Bilezikjian, L.M. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 1987, 328, 175–178.
• 11.
  Zhang, X.; Odom, D.T.; Koo, S.H.; et al. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 4459–4464.
• 12.
  Shaywitz, A.J.; Greenberg, M.E. CREB: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 1999, 68, 821–861.
• 13.
  Srinivasan, S.; Totiger, T.; Shi, C.; et al. Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer. Cancer Res. 2018, 78, 6146–6158.
• 14.
  Felinski, E.A.; Quinn, P.G. The coactivator dTAF(II)110/hTAF(II)135 is sufficient to recruit a polymerase complex and activate basal transcription mediated by CREB. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 13078–13083.
• 15.
  Mayr, B.M.; Guzman, E.; Montminy, M. Glutamine rich and basic region/leucine zipper (bZIP) domains stabilize cAMP-response element-binding protein (CREB) binding to chromatin. J. Biol. Chem. 2005, 280, 15103–15110.
• 16.
  Schumacher, M.A.; Goodman, R.H.; Brennan, R.G. The structure of a CREB bZIP. somatostatin CRE complex reveals the basis for selective dimerization and divalent cation-enhanced DNA binding. J. Biol. Chem. 2000, 275, 35242–35247.
• 17.
  Dou, Y.; Kawaler, E.A.; Zhou, D.C.; et al. Proteogenomic Characterization of Endometrial Carcinoma. Cell 2020, 180, 729–748.e726.
• 18.
  Abida, W.; Cyrta, J.; Heller, G.; et al. Genomic correlates of clinical outcome in advanced prostate cancer. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 11428–11436.
• 19.
  Ghandi, M.; Huang, F.W.; Jané-Valbuena, J.; et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature 2019, 569, 503–508.
• 20.
  Sloan, E.A.; Chiang, J.; Villanueva-Meyer, J.E.; et al. Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms. Brain Pathol. 2021, 31, e12918.
• 21.
  Hill, M.; Tran, N. miRNA interplay: Mechanisms and consequences in cancer. Dis. Model Mech. 2021, 14, dmm047662.
• 22.
  Tan, X.; Wang, S.; Yang, B.; et al. The CREB-miR-9 negative feedback minicircuitry coordinates the migration and proliferation of glioma cells. PLoS ONE 2012, 7, e49570.
• 23.
  Cohen, P. The origins of protein phosphorylation. Nat. Cell Biol. 2002, 4, E127–E130.
• 24.
  Johannessen, M.; Delghandi, M.P.; Moens, U. What turns CREB on? Cell. Signalling 2004, 16, 1211–1227.
• 25.
  Thakur, J.K.; Yadav, A.; Yadav, G. Molecular recognition by the KIX domain and its role in gene regulation. Nucleic Acids Res. 2014, 42, 2112–2125.
• 26.
  Shaywitz, A.J.; Dove, S.L.; Kornhauser, J.M.; et al. Magnitude of the CREB-dependent transcriptional response is determined by the strength of the interaction between the kinase-inducible domain of CREB and the KIX domain of CREB-binding protein. Mol. Cell. Biol. 2000, 20, 9409–9422.
• 27.
  Chrivia, J.C.; Kwok, R.P.; Lamb, N.; et al. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1993, 365, 855–859.
• 28.
  Balogh, A.; Németh, M.; Koloszár, I.; et al. Overexpression of CREB protein protects from tunicamycin-induced apoptosis in various rat cell types. Apoptosis 2014, 19, 1080–1098.
• 29.
  Niederberger, E.; Ehnert, C.; Gao, W.; et al. The impact of CREB and its phosphorylation at Ser142 on inflammatory nociception. Biochem. Biophys. Res. Commun. 2007, 362, 75–80.
• 30.
  Shanware, N.P.; Trinh, A.T.; Williams, L.M.; et al. Coregulated ataxia telangiectasia-mutated and casein kinase sites modulate cAMP-response element-binding protein-coactivator interactions in response to DNA damage. J. Biol. Chem. 2007, 282, 6283–6291.
• 31.
  Shanware, N.P.; Williams, L.M.; Bowler, M.J.; et al. Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190. BMB Rep. 2009, 42, 142–147.
• 32.
  Pan, S.; Chen, R. Pathological implication of protein post-translational modifications in cancer. Mol. Aspects. Med. 2022, 86, 101097.
• 33.
  Steven, A.; Friedrich, M.; Jank, P.; et al. What turns CREB on? And off? And why does it matter? Cell. Mol. Life Sci. 2020, 77, 4049–4067.
• 34.
  Lu, S.; Yin, X.; Wang, J.; et al. SIRT1 regulates O-GlcNAcylation of tau through OGT. Aging 2020, 12, 7042–7055.
• 35.
  Liu, X.F.; Tang, C.X.; Zhang, L.; et al. Down-Regulated CUEDC2 Increases GDNF Expression by Stabilizing CREB Through Reducing Its Ubiquitination in Glioma. Neurochem. Res. 2020, 45, 2915–2925.
• 36.
  Zhang, N.; Shi, L.; Wang, Y. CREB-associated glycosylation and function in human disease. Adv. Clin. Exp. Med. 2022, 31, 1289–1297.
• 37.
  Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57–70.
• 38.
  Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discov. 2022, 12, 31–46.
• 39.
  Cheng, N.; Chytil, A.; Shyr, Y.; et al. Transforming growth factor-beta signaling-deficient fibroblasts enhance hepatocyte growth factor signaling in mammary carcinoma cells to promote scattering and invasion. Mol. Cancer Res. 2008, 6, 1521–1533.
• 40.
  Ansari, K.M.; Rundhaug, J.E.; Fischer, S.M. Multiple signaling pathways are responsible for prostaglandin E2-induced murine keratinocyte proliferation. Mol. Cancer Res. 2008, 6, 1003–1016.
• 41.
  Linder, M.; Glitzner, E.; Srivatsa, S.; et al. EGFR is required for FOS-dependent bone tumor development via RSK2/CREB signaling. EMBO Mol. Med. 2018, 10, e9408.
• 42.
  Wan, X.; Zhou, M.; Huang, F.; et al. AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development. Cell Death Dis. 2021, 12, 172.
• 43.
  Adams, J.M.; Cory, S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007, 26, 1324–1337.
• 44.
  Walia, M.K.; Ho, P.M.; Taylor, S.; et al. Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance. Elife 2016, 5, e13446.
• 45.
  Walia, M.K.; Taylor, S.; Ho, P.W.M.; et al. Tolerance to sustained activation of the cAMP/Creb pathway activity in osteoblastic cells is enabled by loss of p53. Cell Death Dis. 2018, 9, 844.
• 46.
  Wang, H.; Ren, R.; Yang, Z.; et al. The COL11A1/Akt/CREB signaling axis enables mitochondrial-mediated apoptotic evasion to promote chemoresistance in pancreatic cancer cells through modulating BAX/BCL-2 function. J. Cancer 2021, 12, 1406–1420.
• 47.
  Levy, J.M.M.; Towers, C.G.; Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer 2017, 17, 528–542.
• 48.
  Chen, S.J.; Bao, L.; Keefer, K.; et al. Transient receptor potential ion channel TRPM2 promotes AML proliferation and survival through modulation of mitochondrial function, ROS, and autophagy. Cell Death Dis. 2020, 11, 247.
• 49.
  Wang, M.; Liu, K.; Bu, H.; et al. Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy. Mol. Ther. Oncolytics 2022, 26, 314–329.
• 50.
  Fares, J.; Fares, M.Y.; Khachfe, H.H.; et al. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct Target Ther. 2020, 5, 28.
• 51.
  Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
• 52.
  Xu, X.; Zhu, Y.; Liang, Z.; et al. c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial-mesenchymal transition in bladder cancer by regulating Akt/GSK-3β/Snail signaling. Cell Death Dis. 2016, 7, e2088.
• 53.
  Wu, D.; Zhau, H.E.; Huang, W.C.; et al. cAMP-responsive element-binding protein regulates vascular endothelial growth factor expression: Implication in human prostate cancer bone metastasis. Oncogene 2007, 26, 5070–5077.
• 54.
  Karamanos, N.‍K.; Theocharis, A.‍D.; Piperigkou, Z.; et al. A guide to the composition and functions of the extracellular matrix. FEBS J. 2021, 288, 6850–6912.
• 55.
  Kessenbrock, K.; Plaks, V.; Werb, Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 2010, 141, 52–67.
• 56.
  Park, J.K.; Park, S.H.; So, K.; et al. ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB. Int. J. Oncol. 2010, 36, 181–192.
• 57.
  Li, J.; Liu, X.; Wang, W.; et al. MSK1 promotes cell proliferation and metastasis in uveal melanoma by phosphorylating CREB. Arch. Med. Sci. 2020, 16, 1176–1188.
• 58.
  Meng, X.Y.; Zhang, H.Z.; Ren, Y.Y.; et al. Pinin promotes tumor progression via activating CREB through PI3K/AKT and ERK/MAPK pathway in prostate cancer. Am. J. Cancer Res. 2021, 11, 1286–1303.
• 59.
  Hu, S.; Wang, L.; Zhang, X.; et al. Autophagy induces transforming growth factor-‍β‍-dependent epithelial-mesenchymal transition in hepatocarcinoma cells through cAMP response element binding signalling. J. Cell Mol. Med. 2018, 22, 5518–5532.
• 60.
  Fujishita, T.; Kojima, Y.; Kajino-Sakamoto, R.; et al. The cAMP/PKA/CREB and TGFβ/SMAD4 Pathways Regulate Stemness and Metastatic Potential in Colorectal Cancer Cells. Cancer Res. 2022, 82, 4179–4190.
• 61.
  Viallard, C.; Larrivée, B. Tumor angiogenesis and vascular normalization: Alternative therapeutic targets. Angiogenesis 2017, 20, 409–426.
• 62.
  Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 2019, 176, 1248–1264.
• 63.
  Zhao, D.; Desai, S.; Zeng, H. VEGF stimulates PKD-mediated CREB-dependent orphan nuclear receptor Nurr1 expression: Role in VEGF-induced angiogenesis. Int. J. Cancer 2011, 128, 2602–2612.
• 64.
  Kaur, S.; Bronson, S.M.; Pal-Nath, D.; et al. Functions of Thrombospondin-1 in the Tumor Microenvironment. Int. J. Mol. Sci. 2021, 22, 4570.
• 65.
  Hulsurkar, M.; Li, Z.; Zhang, Y.; et al. Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1. Oncogene 2017, 36, 1525–1536.
• 66.
  Zhang, Y.; Zheng, D.; Zhou, T.; et al. Androgen deprivation promotes neuroendocrine differentiation and angiogenesis through CREB-EZH2-TSP1 pathway in prostate cancers. Nat. Commun. 2018, 9, 4080.
• 67.
  Meyuhas, R.; Pikarsky, E.; Tavor, E.; et al. A Key role for cyclic AMP-responsive element binding protein in hypoxia-mediated activation of the angiogenesis factor CCN1 (CYR61) in Tumor cells. Mol. Cancer Res. 2008, 6, 1397–1409.
• 68.
  Dobroff, A.S.; Wang, H.; Melnikova, V.O.; et al. Silencing cAMP-response element-binding protein (CREB) identifies CYR61 as a tumor suppressor gene in melanoma. J. Biol. Chem. 2009, 284, 26194–26206.
• 69.
  Park, J.H.; Pyun, W.Y.; Park, H.W. Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets. Cells 2020, 9, 2308.
• 70.
  Liberti, M.V.; Locasale, J.W. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem. Sci. 2016, 41, 211–218.
• 71.
  Vaupel, P.; Schmidberger, H.; Mayer, A. The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression. Int. J. Radiat. Biol. 2019, 95, 912–919.
• 72.
  Liu, Z.; Chen, X.; Wang, Y.; et al. PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade. J. Biol. Chem. 2014, 289, 29739–29749.
• 73.
  Gao, R.; Li, D.; Xun, J.; et al. CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism. Theranostics 2018, 8, 6248–6262.
• 74.
  Kuo, M.H.; Chang, W.W.; Yeh, B.W.; et al. Glucose Transporter 3 is Essential for the Survival of Breast Cancer Cells in the Brain. Cells 2019, 8, 1568.
• 75.
  Yu, T.; Yang, G.; Hou, Y.; et al. Cytoplasmic GPER translocation in cancer-associated fibroblasts mediates cAMP/PKA/CREB/glycolytic axis to confer tumor cells with multidrug resistance. Oncogene 2017, 36, 2131–2145.
• 76.
  Xing, F.; Luan, Y.; Cai, J.; et al. The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes. Cell Rep. 2018, 23, 2832–2833.
• 77.
  Dunn, G.P.; Bruce, A.T.; Ikeda, H.; et al. Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol. 2002, 3, 991–998.
• 78.
  Swann, J.B.; Smyth, M.J. Immune surveillance of tumors. J. Clin. Invest. 2007, 117, 1137–1146.
• 79.
  Jayasingam, S.D.; Citartan, M.; Thang, T.H.; et al. Evaluating the Polarization of Tumor-Associated Macrophages into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice. Front. Oncol. 2019, 9, 1512.
• 80.
  Jiang, H.; Wei, H.; Wang, H.; et al. Zeb1-induced metabolic reprogramming of glycolysis is essential for macrophage polarization in breast cancer. Cell Death Dis. 2022, 13, 206.
• 81.
  Cheng, Y.; Zhu, Y.; Xu, J.; et al. PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway. Mol. Cancer 2018, 17, 13.
• 82.
  Sun, C.; Wang, B.; Hao, S. Adenosine-A2A Receptor Pathway in Cancer Immunotherapy. Front. Immunol. 2022, 13, 837230.
• 83.
  Mastelic-Gavillet, B.; Navarro Rodrigo, B.; Décombaz, L.; et al. Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8(+) T cells. J. Immunother Cancer 2019, 7, 257.
• 84.
  Masjedi, A.; Hassannia, H.; Atyabi, F.; et al. Downregulation of A2AR by siRNA loaded PEG-chitosan-lactate nanoparticles restores the T cell mediated anti-tumor responses through blockage of PKA/CREB signaling pathway. Int. J. Biol. Macromol. 2019, 133, 436–445.
• 85.
  Dziedzic, K.; Węgrzyn, P.; Gałęzowski, M.; et al. Release of adenosine-induced immunosuppression: Comprehensive characterization of dual A(2A)/A(2B) receptor antagonist. Int. Immunopharmacol. 2021, 96, 107645.
• 86.
  Sauer, M.; Schuldner, M.; Hoffmann, N.; et al. CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells. Oncogene 2017, 36, 933–941.
• 87.
  Newton, K.; Dixit, V.M. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect. Biol. 2012, 4, a006049. doi:10.1101/cshperspect.a006049 From NLM.
• 88.
  Wen, A.Y.; Sakamoto, K.M.; Miller, L.S. The role of the transcription factor CREB in immune function. J. Immunol. 2010, 185, 6413–6419.
• 89.
  Westbom, C.M.; Shukla, A.; MacPherson, M.B.; et al. CREB-induced inflammation is important for malignant mesothelioma growth. Am. J. Pathol. 2014, 184, 2816–2827.
• 90.
  Pan, P.; Oshima, K.; Huang, Y.W.; et al. Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors. Int. J. Cancer 2018, 143, 886–896.
• 91.
  Resende, C.; Regalo, G.; Durães, C.; et al. Interleukin-1B signalling leads to increased survival of gastric carcinoma cells through a CREB-C/EBPβ-associated mechanism. Gastric Cancer 2016, 19, 74–84.
• 92.
  Lapidot, T.; Sirard, C.; Vormoor, J.; et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994, 367, 645–648.
• 93.
  Zhou, G.; Latchoumanin, O.; Bagdesar, M.; et al. Aptamer-Based Therapeutic Approaches to Target Cancer Stem Cells. Theranostics 2017, 7, 3948–3961.
• 94.
  Daniel, P.M.; Filiz, G.; Brown, D.V.; et al. PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding protein. Neuro. Oncol. 2018, 20, 1344–1355.
• 95.
  Duan, S.; Yuan, G.; Liu, X.; et al. PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype. Nat. Commun. 2015, 6, 10068.
• 96.
  Eyre, R.; Alférez, D.G.; Santiago-Gómez, A.; et al. Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling. Nat. Commun. 2019, 10, 5016.
• 97.
  Zhang, Z.; Qiu, N.; Yin, J.; et al. SRGN crosstalks with YAP to maintain chemoresistance and stemness in breast cancer cells by modulating HDAC2 expression. Theranostics 2020, 10, 4290–4307.
• 98.
  Lv, Y.; Cang, W.; Li, Q.; et al. Erlotinib overcomes paclitaxel-resistant cancer stem cells by blocking the EGFR-CREB/GRβ-IL-6 axis in MUC1-positive cervical cancer. Oncogenesis 2019, 8, 70.
• 99.
  Pigazzi, M.; Manara, E.; Baron, E.; et al. ICER expression inhibits leukemia phenotype and controls tumor progression. Leukemia 2008, 22, 2217–2225.
• 100.
  Molina, C.A.; Foulkes, N.S.; Lalli, E.; et al. Inducibility and negative autoregulation of CREM: An alternative promoter directs the expression of ICER, an early response repressor. Cell 1993, 75, 875–886.
• 101.
  Xie, S.; Price, J.E.; Luca, M.; et al. Dominant-negative CREB inhibits tumor growth and metastasis of human melanoma cells. Oncogene 1997, 15, 2069–2075.
• 102.
  Zhang, H.; Yang, S.; Wang, J.; et al. Blockade of AMPK-Mediated cAMP-PKA-CREB/ATF1 Signaling Synergizes with Aspirin to Inhibit Hepatocellular Carcinoma. Cancers 2021, 13, 1738.
• 103.
  Pigazzi, M.; Manara, E.; Baron, E.; et al. miR-34b targets cyclic AMP-responsive element binding protein in acute myeloid leukemia. Cancer Res. 2009, 69, 2471–2478.
• 104.
  Illiano, M.; Nigro, E.; Sapio, L.; et al. Adiponectin down-regulates CREB and inhibits proliferation of A549 lung cancer cells. Pulm. Pharmacol. Ther. 2017, 45, 114–120.
• 105.
  Best, J.L.; Amezcua, C.A.; Mayr, B.; et al. Identification of small-molecule antagonists that inhibit an activator: Coactivator interaction. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 17622–17627.
• 106.
  De Guzman, R.N.; Goto, N.K.; Dyson, H.J.; et al. Structural basis for cooperative transcription factor binding to the CBP coactivator. J. Mol. Biol. 2006, 355, 1005–1013.
• 107.
  Uttarkar, S.; Dukare, S.; Bopp, B.; et al. Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300. Mol. Cancer Ther. 2015, 14, 1276–1285.
• 108.
  Sun, H.; Chung, W.C.; Ryu, S.H.; et al. Cyclic AMP-responsive element binding protein- and nuclear factor-kappaB-regulated CXC chemokine gene expression in lung carcinogenesis. Cancer Prev. Res. 2008, 1, 316–328.
• 109.
  Zhu, L.; Zhou, K.X.; Ma, M.Z.; et al. Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation. J. Immunol. Res. 2022, 2022, 1590717.
• 110.
  Steven, A.; Leisz, S.; Massa, C.; et al. HER-2/neu mediates oncogenic transformation via altered CREB expression and function. Mol. Cancer Res. 2013, 11, 1462–1477.
• 111.
  Lee, J.W.; Park, H.S.; Park, S.A.; et al. A Novel Small-Molecule Inhibitor Targeting CREB-CBP Complex Possesses Anti-Cancer Effects along with Cell Cycle Regulation, Autophagy Suppression and Endoplasmic Reticulum Stress. PLoS ONE 2015, 10, e0122628.
• 112.
  Li, B.X.; Xiao, X. Discovery of a small-molecule inhibitor of the KIX-KID interaction. Chembiochem 2009, 10, 2721–2724.
• 113.
  Li, B.X.; Yamanaka, K.; Xiao, X. Structure-activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription. Bioorg. Med. Chem. 2012, 20, 6811–6820.
• 114.
  Jiang, M.; Yan, Y.; Yang, K.; et al. Small molecule nAS-E targeting cAMP response element binding protein (CREB) and CREB-binding protein interaction inhibits breast cancer bone metastasis. J. Cell Mol. Med. 2019, 23, 1224–1234.
• 115.
  Li, B.X.; Gardner, R.; Xue, C.; et al. Systemic Inhibition of CREB is Well-tolerated in vivo. Sci. Rep. 2016, 6, 34513.
• 116.
  Xie, F.; Li, B.X.; Kassenbrock, A.; et al. Identification of a Potent Inhibitor of CREB-Mediated Gene Transcription with Efficacious in Vivo Anticancer Activity. J. Med. Chem. 2015, 58, 5075–5087.
• 117.
  Xie, F.; Fan, Q.; Li, B.X.; et al. Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription with 666-15. J. Med. Chem. 2019, 62, 11423–11429.
• 118.
  Peng, J.; Miller, M.; Li, B.X.; et al. Design, Synthesis and Biological Evaluation of Prodrugs of 666-15 as Inhibitors of CREB-Mediated Gene Transcription. ACS Med. Chem. Lett. 2022, 13, 388–395.
• 119.
  Mitton, B.; Chae, H.D.; Hsu, K.; et al. Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells. Leukemia 2016, 30, 2302–2311.
• 120.
  Chae, H.D.; Cox, N.; Capolicchio, S.; et al. SAR optimization studies on modified salicylamides as a potential treatment for acute myeloid leukemia through inhibition of the CREB pathway. Bioorg. Med. Chem. Lett. 2019, 29, 2307–2315.
• 121.
  Vinson, C.; Myakishev, M.; Acharya, A.; et al. Classification of human B-ZIP proteins based on dimerization properties. Mol. Cell Biol. 2002, 22, 6321–6335.
• 122.
  Rishi, V.; Potter, T.; Laudeman, J.; et al. A high-throughput fluorescence-anisotropy screen that identifies small molecule inhibitors of the DNA binding of B-ZIP transcription factors. Anal. Biochem. 2005, 340, 259–271.
• 123.
  Zhao, J.; Stagno, J.R.; Varticovski, L.; et al. P6981, an arylstibonic acid, is a novel low nanomolar inhibitor of cAMP response element-binding protein binding to DNA. Mol. Pharmacol. 2012, 82, 814–823.
• 124.
  Cho, Y.S.; Kim, M.K.; Cheadle, C.; et al. A genomic-scale view of the cAMP response element-enhancer decoy: A tumor target-based genetic tool. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15626–15631.
• 125.
  Park, S.I.; Park, S.J.; Lee, J.; et al. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity. Biochem. Biophys. Res. Commun. 2016, 469, 363–369.
• 126.
  Uchida, D.; Saito, Y.; Kikuchi, S.; et al. Development of gene therapy with a cyclic adenosine monophosphate response element decoy oligodeoxynucleotide to prevent vascular intimal hyperplasia. J. Vasc. Surg. 2020, 71, 229–241.
• 127.
  Chowdhury, M.A.R.; An, J.; Jeong, S. The Pleiotropic Face of CREB Family Transcription Factors. Mol. Cells 2023, 46, 399–413.
• 128.
  Dinevska, M.; Widodo, S.S.; Cook, L.; et al. CREB: A multifaceted transcriptional regulator of neural and immune function in CNS tumors. Brain Behav. Immun. 2024, 116, 140–149.
• 129.
  Teich, A.F.; Nicholls, R.E.; Puzzo, D.; et al. Synaptic therapy in Alzheimer’s disease: A CREB-centric approach. Neurotherapeutics 2015, 12, 29–41.