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Article

Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway

  • Authors:
    • Dong Uk Kim
    • Jehyun Nam
    • Matthew D. Cha
    • Sang‑Woo Kim
  • View Affiliations / Copyright

    Affiliations: Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea, Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA
  • Pages: 3589-3598
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    Published online on: January 31, 2019
       https://doi.org/10.3892/ol.2019.9996
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Abstract

Colorectal cancer (CRC) is a complex disease involving numerous genetic abnormalities. One of the major characteristics of CRC is enhanced Wnt signaling caused by loss‑of‑function mutations in the adenomatous polyposis coli (APC) gene. Previously, it has been demonstrated that the majority of malignant phenotypes following APC deletion in adult murine small intestines could be rescued when Myc, a downstream target of the Wnt pathway, was deleted. This indicated that Myc is a critical regulator of CRC development following APC loss. Previous studies reported that cyclic adenosine 3',5'‑monophosphate (cAMP) can influence the AKT/mammalian target of rapamycin (mTOR) survival pathway in cancer and Myc is a critical downstream molecule of AKT/mTOR signaling. Phosphodiesterase 4D (PDE4D), a member of the cAMP‑specific PDE4 family, has been associated with drug resistance in CRC. However, the association between PDE4D and Myc remains unclear. To investigate the potential role of PDE4D in Myc regulation in CRC, the present study evaluated the expression levels of PDE4 subtypes in DLD‑1 CRC cells. Additionally, the effects of PDE4 inhibitors on Myc expression and oncogenic properties were analyzed by western blot analysis, reverse transcription‑quantitative polymerase chain reaction, colony formation and soft agar assays. It was demonstrated that cAMP/PDE4D signals serve a critical role in regulating Myc expression in DLD‑1 CRC cells. Furthermore, PDE4D was identified to be a main hydrolyzer of cAMP and suppression of PDE4D using selective inhibitors of PDE4 increased intracellular cAMP levels, which resulted in a marked decrease in the oncogenic properties of DLD‑1 cells, including colony formation, cell proliferation and anchorage‑independent growth. Notably, the current data imply that cAMP represses Myc expression via the downregulation of AKT/mTOR signaling, which was abolished by high PDE4D activities in DLD‑1 cells. Additionally, a natural polyphenol resveratrol in combination with forskolin elevated the concentration of cAMP and enhanced the expression of Myc and the malignant phenotype of DLD‑1 cells, reproducing the effect of known chemical inhibitors of PDE4. In conclusion, the present study identified that cAMP/PDE4D signaling is a critical regulator of Myc expression in DLD‑1 and possibly other CRC cells.
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1 

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global patterns and trends in colorectal cancer incidence and mortality. Gut. 66:683–691. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Miller KD and Jemal A: Colorectal cancer mortality rates in adults aged 20 to 54 years in the united states, 1970–2014. JAMA. 318:572–574. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Worthley DL and Leggett BA: Colorectal cancer: Molecular features and clinical opportunities. Clin Biochem Rev. 31:31–38. 2010.PubMed/NCBI

4 

Hinoue T, Weisenberger DJ, Pan F, Campan M, Kim M, Young J, Whitehall VL, Leggett BA and Laird PW: Analysis of the association between CIMP and BRAF in colorectal cancer by DNA methylation profiling. PLoS One. 4:e83572009. View Article : Google Scholar : PubMed/NCBI

5 

Mundade R, Imperiale TF, Prabhu L, Loehrer PJ and Lu T: Genetic pathways, prevention, and treatment of sporadic colorectal cancer. Oncoscience. 1:400–406. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I and Kerr D: Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer. 9:489–499. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Fodde R: The APC gene in colorectal cancer. Eur J Cancer. 38:867–871. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Schneikert J and Behrens J: The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut. 56:417–425. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, Wiesmann M, Garcia PD, Fuller JH, Chan V, et al: Beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res. 63:3145–3153. 2003.PubMed/NCBI

10 

Herbst A, Jurinovic V, Krebs S, Thieme SE, Blum H, Göke B and Kolligs FT: Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling. BMC Genomics. 15:742014. View Article : Google Scholar : PubMed/NCBI

11 

Morin PJ: Beta-catenin signaling and cancer. Bioessays. 21:1021–1030. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Sansom OJ, Meniel VS, Muncan V, Phesse TJ, Wilkins JA, Reed KR, Vass JK, Athineos D and Clevers H: Myc deletion rescues Apc deficiency in the small intestine. Nature. 446:676–679. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Sewastianik T, Prochorec-Sobieszek M, Chapuy B and Juszczyński P: MYC deregulation in lymphoid tumors: Molecular mechanisms, clinical consequences and therapeutic implications. Biochim Biophys Acta. 1846:457–467. 2014.PubMed/NCBI

14 

Rall TW and Sutherland EW: Formation of a cyclic adenine ribonucleotide by tissue particles. J Biol Chem. 232:1065–1076. 1958.PubMed/NCBI

15 

Sutherland EW and Rall TW: Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem. 232:1077–1091. 1958.PubMed/NCBI

16 

Daniel PB, Walker WH and Habener JF: Cyclic AMP signaling and gene regulation. Annu Rev Nutr. 18:353–383. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Fimia GM and Sassone-Corsi P: Cyclic AMP signalling. J Cell Sci. 114:1971–1972. 2001.PubMed/NCBI

18 

Sassone-Corsi P: The cyclic AMP pathway. Cold Spring Harb Perspect Biol. 4(a011148)2012.PubMed/NCBI

19 

Kim SW, Rai D and Aguiar RC: Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B control of glucocorticoid response in B-cell lymphoma. Clin Cancer Res. 17:6723–6732. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Smith PG, Wang F, Wilkinson KN, Savage KJ, Klein U, Neuberg DS, Bollag G, Shipp MA and Aguiar RC: The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma. Blood. 105:308–316. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Tsunoda T, Ota T, Fujimoto T, Doi K, Tanaka Y, Yoshida Y, Ogawa M, Matsuzaki H, Hamabashiri M, Tyson DR, et al: Inhibition of phosphodiesterase-4 (PDE4) activity triggers luminal apoptosis and AKT dephosphorylation in a 3-D colonic-crypt model. Mol Cancer. 11:462012. View Article : Google Scholar : PubMed/NCBI

23 

Cao B, Wang K, Liao JM, Zhou X, Liao P, Zeng SX, He M, Chen L, He Y, Li W and Lu H: Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation. Elife. 5(e15978)2016.

24 

Lakics V, Karran EH and Boess FG: Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology. 59:367–374. 2010. View Article : Google Scholar : PubMed/NCBI

25 

McEwan DG, Brunton VG, Baillie GS, Leslie NR, Houslay MD and Frame MC: Chemoresistant KM12C colon cancer cells are addicted to low cyclic AMP levels in a phosphodiesterase 4-regulated compartment via effects on phosphoinositide 3-kinase. Cancer Res. 67:5248–5257. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Le Jeune IR, Shepherd M, Van Heeke G, Houslay MD and Hall IP: Cyclic AMP-dependent transcriptional up-regulation of phosphodiesterase 4D5 in human airway smooth muscle cells. Identification and characterization of a novel PDE4D5 promoter. J Biol Chem. 277:35980–35989. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Takahashi M, Terwilliger R, Lane C, Mezes PS, Conti M and Duman RS: Chronic antidepressant administration increases the expression of cAMP-specific phosphodiesterase 4A and 4B isoforms. J Neurosci. 19:610–618. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Lipworth BJ: Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet. 365:167–175. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Francipane MG and Lagasse E: mTOR pathway in colorectal cancer: An update. Oncotarget. 5:49–66. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Pandurangan AK: Potential targets for prevention of colorectal cancer: A focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev. 14:2201–2205. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Sipos F, Firneisz G and Műzes G: Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases. World J Gastroenterol. 22:7938–7950. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Pirson I, Coulonval K, Lamy F and Dumont JE: c-Myc expression is controlled by the mitogenic cAMP-cascade in thyrocytes. J Cell Physiol. 168:59–70. 1996. View Article : Google Scholar : PubMed/NCBI

33 

Williamson EA, Burgess GS, Eder P, Litz-Jackson S and Boswell HS: Cyclic AMP negatively controls c-myc transcription and G1 cell cycle progression in p210 BCR-ABL transformed cells: Inhibitory activity exerted through cyclin D1 and cdk4. Leukemia. 11:73–85. 1997. View Article : Google Scholar : PubMed/NCBI

34 

Di Costanzo A, Del Gaudio N, Migliaccio A and Altucci L: Epigenetic drugs against cancer: An evolving landscape. Arch Toxicol. 88:651–668. 2014. View Article : Google Scholar

35 

Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, et al: Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 148:421–433. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Tsunoda T, Ishikura S, Doi K, Matsuzaki H, Iwaihara Y and Shirasawa S: Resveratrol induces luminal apoptosis of human colorectal cancer HCT116 cells in three-dimensional culture. Anticancer Res. 34:4551–4555. 2014.PubMed/NCBI

37 

Goldhoff P, Warrington NM, Limbrick DD Jr, Hope A, Woerner BM, Jackson E, Perry A, Piwnica-Worms D and Rubin JB: Targeted inhibition of cyclic AMP phosphodiesterase-4 promotes brain tumor regression. Clin Cancer Res. 14:7717–7725. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Ogawa R, Streiff MB, Bugayenko A and Kato GJ: Inhibition of PDE4 phosphodiesterase activity induces growth suppression, apoptosis, glucocorticoid sensitivity, p53, and p21(WAF1/CIP1) proteins in human acute lymphoblastic leukemia cells. Blood. 99:3390–3397. 2002. View Article : Google Scholar : PubMed/NCBI

39 

Scott PH and Lawrence JC Jr: Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3-L1 adipocytes. J Biol Chem. 273:34496–34501. 1998. View Article : Google Scholar : PubMed/NCBI

40 

Blancquaert S, Wang L, Paternot S, Coulonval K, Dumont JE, Harris TE and Roger PP: cAMP-dependent activation of mammalian target of rapamycin (mTOR) in thyroid cells. Implication in mitogenesis and activation of CDK4. Mol Endocrinol. 24:1453–1468. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Kelly K, Mejia A, Suhasini AN, Lin AP, Kuhn J, Karnad AB, Weitman S and Aguiar RC: Safety and pharmacodynamics of the PDE4 inhibitor roflumilast in advanced B-cell malignancies. Clin Cancer Res. 23:1186–1192. 2017. View Article : Google Scholar : PubMed/NCBI

42 

Delyon J, Servy A, Laugier F, André J, Ortonne N, Battistella M, Mourah S, Bensussan A, Lebbé C and Dumaz N: PDE4D promotes FAK-mediated cell invasion in BRAF-mutated melanoma. Oncogene. 36:3252–3262. 2017. View Article : Google Scholar : PubMed/NCBI

43 

Ge X, Milenkovic L, Suyama K, Hartl T, Purzner T, Winans A, Meyer T and Scott MP: Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma. Elife. 4:e070682015. View Article : Google Scholar

44 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

45 

Bruno O, Fedele E, Prickaerts J, Parker LA, Canepa E, Brullo C, Cavallero A, Gardella E, Balbi A, Domenicotti C, et al: GEBR-7b, a novel PDE4D selective inhibitor that improves memory in rodents at non-emetic doses. Br J Pharmacol. 164:2054–2063. 2011. View Article : Google Scholar : PubMed/NCBI

46 

Ricciarelli R, Brullo C, Prickaerts J, Arancio O, Villa C, Rebosio C, Calcagno E, Balbi M, van Hagen BT, Argyrousi EK, et al: Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer's disease. Sci Rep. 7:463202017. View Article : Google Scholar : PubMed/NCBI

47 

Mishra RR, Belder N, Ansari SA, Kayhan M, Bal H, Raza U, Ersan PG, Tokat ÜM, Eyüpoğlu E, Saatci Ö, et al: Reactivation of cAMP pathway by PDE4D inhibition represents a novel druggable axis for overcoming tamoxifen resistance in ER-positive breast cancer. Clin Cancer Res. 24:1987–2001. 2018. View Article : Google Scholar : PubMed/NCBI

48 

Böttcher R, Dulla K, van Strijp D, Dits N, Verhoef EI, Baillie GS, van Leenders GJ, Houslay MD, Jenster G and Hoffmann R: Human PDE4D isoform composition is deregulated in primary prostate cancer and indicative for disease progression and development of distant metastases. Oncotarget. 7:70669–70684. 2016. View Article : Google Scholar : PubMed/NCBI

49 

Li Q, Liang X, Wang Y, Meng X, Xu Y, Cai S, Wang Z, Liu J and Cai G: miR-139-5p inhibits the epithelial-mesenchymal transition and enhances the chemotherapeutic sensitivity of colorectal cancer cells by downregulating BCL2. Sci Rep. 6:271572016. View Article : Google Scholar : PubMed/NCBI

50 

Garcia-Morales V, Luaces-Regueira M and Campos-Toimil M: The cAMP effectors PKA and Epac activate endothelial NO synthase through PI3K/Akt pathway in human endothelial cells. Biochem Pharmacol. 145:94–101. 2017. View Article : Google Scholar : PubMed/NCBI

51 

Miklos W, Heffeter P, Pirker C, Hager S, Kowol CR, van Schoonhoven S, Stojanovic M, Keppler BK and Berger W: Loss of phosphodiesterase 4D mediates acquired triapine resistance via Epac-Rap1-Integrin signaling. Oncotarget. 7:84556–84574. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kim DU, Nam J, Cha MD and Kim SW: Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway. Oncol Lett 17: 3589-3598, 2019.
APA
Kim, D.U., Nam, J., Cha, M.D., & Kim, S. (2019). Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway. Oncology Letters, 17, 3589-3598. https://doi.org/10.3892/ol.2019.9996
MLA
Kim, D. U., Nam, J., Cha, M. D., Kim, S."Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway". Oncology Letters 17.3 (2019): 3589-3598.
Chicago
Kim, D. U., Nam, J., Cha, M. D., Kim, S."Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway". Oncology Letters 17, no. 3 (2019): 3589-3598. https://doi.org/10.3892/ol.2019.9996
Copy and paste a formatted citation
x
Spandidos Publications style
Kim DU, Nam J, Cha MD and Kim SW: Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway. Oncol Lett 17: 3589-3598, 2019.
APA
Kim, D.U., Nam, J., Cha, M.D., & Kim, S. (2019). Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway. Oncology Letters, 17, 3589-3598. https://doi.org/10.3892/ol.2019.9996
MLA
Kim, D. U., Nam, J., Cha, M. D., Kim, S."Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway". Oncology Letters 17.3 (2019): 3589-3598.
Chicago
Kim, D. U., Nam, J., Cha, M. D., Kim, S."Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD‑1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway". Oncology Letters 17, no. 3 (2019): 3589-3598. https://doi.org/10.3892/ol.2019.9996
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