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The Wnt Pathway Target Gene CCND1 Changes Mitochondrial Localization and Decreases Mitochondrial Activity in Colorectal Cancer Cell Line SW480

DOI: 10.4236/jbm.2016.412017, PP. 132-143

Keywords: ATP, Cyclin D1, Colorectal Cancer, Mitochondria, Wnt

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Abstract:

Mutations leading to constitutive activation of the Wnt pathway and its target genes are frequently observed in cancer. The Wnt pathway promotes cell proliferation and increasing evidence supports its role also in cancer cell metabolism. This study aims to elucidate the role of the Wnt/β-catenin target gene CCND1 in these processes in colorectal cancer. We analyzed whether knock-down of CCND1 affects cell cycle progression and energy metabolism in a colorectal cancer cell line. Down-regulation of CCND1 led to retardation of the cell cycle. The proportion of cells in the G0 phase increased, while the amount of cells in the S- and G2/M phase decreased. Interestingly, knock-down of CCND1 changed the perinuclear localization of mitochondria into a homogeneous distribution within the cytosol. In addition CCND1 knock-down led to an increase of the intracellular ATP level indicating that cyclin D1 reduced mitochondrial activity. Our findings suggest that in addition to its role in cell cycle regulation, the Wnt target gene CCND1 regulates mitochondrial localization and inhibits mitochondrial activity in colorectal cancer cells.

References

[1]  Giles, R.H., van Es, J.H. and Clevers, H. (2003) Caught up in a Wnt Storm: Wnt Signaling in Cancer. Biochimica et Biophysica Acta, 1653, 1-24.
https://doi.org/10.1016/s0304-419x(03)00005-2
[2]  Wend, P., Holland, J.D., Ziebold, U. and Birchmeier, W. (2010) Wnt Signaling in Stem and Cancer Stem Cells. Seminars in Cell & Developmental Biology, 21, 855-863.
https://doi.org/10.1016/j.semcdb.2010.09.004
[3]  Clevers, H. (2006) Wnt/Beta-Catenin Signaling in Development and Disease. Cell, 127, 469-480.
https://doi.org/10.1016/j.cell.2006.10.018
[4]  Vlad, A., Röhrs, S., Klein-Hitpass, L. and Müller, O. (2008) The First Five Years of the Wnt Targetome. Cell Signal, 20, 795-802.
https://doi.org/10.1016/j.cellsig.2007.10.031
[5]  http://www.stanford.edu/group/nusselab/cgi-bin/wnt/
[6]  Tetsu, O. and McCormick, F. (1999) Beta-Catenin Regulates Expression of Cyclin D1 in Colon Carcinoma Cells. Nature, 398, 422-426.
https://doi.org/10.1038/18884
[7]  Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R. and Ben, Ze’ev A. (1999) The Cyclin D1 Gene Is a Target of the Beta-Catenin/LEF-1 Pathway. Proceedings of the National Academy of Sciences of the United States of America, 96. 5522-5527.
https://doi.org/10.1073/pnas.96.10.5522
[8]  Willert, J., Epping, M., Pollack, J.R., Brown, P.O. and Nusse, R. (2002) A Transcriptional Response to Wnt Protein in Human Embryonic Carcinoma Cells. BMC Developmental Biology, 2, 8.
https://doi.org/10.1186/1471-213X-2-8
[9]  van de Wetering, M., Sancho, E., Verweij, C., de Lau, W., Oving, I., Hurlstone, A., van der Haun, K., Batlle, E., Coudreuse, D., Haramis, A.P., Tjon-Pon-Fong, M., Moerer, P., van den Born, M., Soete, G., Pals, S., Eilers, M., Medema, R. and Clevers, H. (2002) The Beta-Catenin/ TCF-4 Complex Imposes a Crypt Progenitor Phenotype on Colorectal Cancer Cells. Cell, 111, 241-250.
https://doi.org/10.1016/S0092-8674(02)01014-0
[10]  Sansom, O.J., Reed, K.R., Hayes, A.J., Ireland, H., Brinkmann, H., Newton, I.P., Batlle, E., Simon-Assmann, P., Clevers, H., Nathke, I.S., Clarke, A.R. and Winton, D.J. (2004) Loss of Apc in Vivo Immediately Perturbs Wnt Signaling, Differentiation, and Migration. Genes & Development, 18, 1385-1390.
https://doi.org/10.1101/gad.287404
[11]  Andreu, P., Colnot, S., Godard, C., Gad, S., Chafey, P., Niwa-Kawakita, M., Laurent-Puig, P., Kahn, A., Robine, S., Perret, C. and Romagnolo, B. (2005) Crypt-Restricted Proliferation and Commitment to the Paneth Cell Lineage Following Apc Loss in the Mouse Intestine. Development, 132, 1443-1451.
https://doi.org/10.1242/dev.01700
[12]  Röhrs, S., Kutzner, N., Vlad, A., Grunwald, T., Ziegler, S. and Müller, O. (2009) Chronological Expression of Wnt Target Genes CCND1, Myc, Cdkn1a, Tfrc, Plf1 and Ramp3. Cell Biology International, 33, 501-508.
https://doi.org/10.1016/j.cellbi.2009.01.016
[13]  Morgan, D.O. (1995) Principles of CDK Regulation. Nature, 374, 131-134.
https://doi.org/10.1038/374131a0
[14]  Matsushime, H., Roussel, M.F. and Sherr, C.J. (1991) Novel Mammalian Cyclins (CYL Genes) Expressed during G1. Cold Spring Harbor Symposia on Quantitative Biology, 56, 69-74.
https://doi.org/10.1101/SQB.1991.056.01.010
[15]  Xiong, Y. and Beach, D. (1991). Population Explosion in the Cyclin Family. Current Biology, 1, 362-364.
https://doi.org/10.1016/0960-9822(91)90193-z
[16]  Pestell, R.G. (2013) New Roles of Cyclin D1. American Journal of Pathology, 183, 3-9.
http://dx.doi.org/10.1016/j.ajpath.2013.03.001
[17]  Sethi, J.K. and Vidal Pluig, A. (2010) Wnt Signalling and the Control of Cellular Metabolism. Biochemical Journal, 427, 1-17.
http://dx.doi.org/10.1042/BJ20091866
[18]  Pate, K.T., Stringari, C., Sprowl-Tanio, S., Wang, K., TeSlaa, T., Hoverter, N.P., McQuade, M.M., Garner, C., Digman, M.A., Teitell, M.A., Edwards, R.A., Gratton, E. and Waterman, M.L. (2014) Wnt Signaling Directs a Metabolic Program of Glycolysis and Angiogenesis in Colon Cancer. EMBO Journal, 33, 1454-1473.
http://dx.doi.org/10.15252/embj.201488598
[19]  Munemitsu, S., Albert, I., Souza, B., Rubinfeld, B. and Polakis, P. (1995) Regulation of Intracellular Beta-Catenin Levels by the Adenomatous Polyposis Coli (APC) Tumor-Suppressor Protein. Proceedings of the National Academy of Sciences of the United States of America, 92, 3046-3050.
http://dx.doi.org/10.1073/pnas.92.7.3046
[20]  Yang, K., Hitomi, M. and Stacey, D.W. (2006) Variations in Cyclin D1 Levels through the Cell Cycle Determine the Proliferative Fate of a Cell. Cell Division, 1, 32.
http://dx.doi.org/10.1186/1747-1028-1-32
[21]  Wang, C., Li, Z., Lu, Y., Du, R., Katiyar, S., Yang, J., Fu, M., Leader, J.E., Quong, A., Novikoff, P.M. and Pestell, R.G. (2006) Cyclin D1 Repression of Nuclear Respiratory Factor 1 Integrates Nuclear DNA Synthesis and Mitochondrial Function. Proceedings of the National Academy of Sciences of the United States of America, 103, 11567-11572.
http://dx.doi.org/10.1073/pnas.0603363103
[22]  Alirol, E. and Martinou, J.C. (2006) Mitochondria and Cancer: Is There a Morphological Connection? Oncogene, 25, 4706-4716.
http://dx.doi.org/10.1038/sj.onc.1209600
[23]  Desagher, S. and Martinou, J.C. (2000) Mitochondria as the Central Control Point of Apoptosis. Trends in Cell Biology, 10, 369-377.
http://dx.doi.org/10.1016/S0962-8924(00)01803-1
[24]  Okamoto, K. and Shaw, J.M. (2005) Mitochondrial Morphology and Dynamics in Yeast and Multicellular Eukaryotes. Annual Review of Genetics, 39, 503-536.
http://dx.doi.org/10.1146/annurev.genet.38.072902.093019
[25]  Warburg, O. (1956) On Respiratory Impairment in Cancer Cells. Science, 124, 269-270.
[26]  Gatenby, R.A. and Gillies, R.J. (2004) Why Do Cancers Have High Aerobic Glycolysis? Nature Reviews Cancer, 4, 891-899.
http://dx.doi.org/10.1038/nrc1478
[27]  Gatenby, R.A. and Gawlinski, E.T. (1996) A Reaction-Diffusion Model of Cancer Invasion. Cancer Research, 56, 5745-5753.
[28]  Schornack, P.A. and Gillies, R.J. (2003) Contributions of Cell Metabolism and H+ Diffusion to the Acidic pH of Tumors. Neoplasia, 5, 135-145.
http://dx.doi.org/10.1016/S1476-5586(03)80005-2
[29]  Sakamaki, T., Casimiro, M.C., Ju, X., Quong, A.A., Katiyar, S., Liu, M., Jiao, X., Li, A., Zhang, X., Lu, Y., Wang, C., Byers, S., Nicholson, R., Link, T., Shemluck, M., Yang, J., Fricke, S.T., Novikoff, P.M., Papanikolaou, A., Arnold, A., Albanese, C. and Pestell, R. (2006) Cyclin D1 Determines Mitochondrial Function in Vivo. Molecular and Cellular Biology, 26, 5449-5469.
http://dx.doi.org/10.1128/MCB.02074-05
[30]  Tchakarska, G., Roussel, M., Troussard, X. and Sola, B. (2011) Cyclin D1 Inhibits Mitochondrial Activity in B Cells. Cancer Research, 71, 1690-1699.
http://dx.doi.org/10.1158/0008-5472.CAN-10-2564
[31]  Bhalla, K., Liu, W.J., Thompson, K., Anders, L., Devarakonda, S., Dewi, R., Buckley, S., Hwang, B.J., Polster, B., Dorsey, S.G., Sun, Y., Sicinski, P. and Girnun, G.D. (2014) Cyclin D1 Represses Gluconeogenesis via Inhibition of the Transcriptional Coactivator PGC1α. Diabetes, 63, 3266-3278.
http://dx.doi.org/10.2337/db13-1283
[32]  Lee, Y., Dominy, J.E., Choi, Y.J., Jurczak, M., Tolliday, N., Camporez, J.P., Chim, H., Lim, J.H., Rua,n H.B., Yang, X., Vazquez, F., Sicinski, P., Shulman, G.I. and Puigserver, P. (2014) Cyclin D1-Cdk4 Controls Glucose Metabolism Independently of Cell Cycle Progression. Nature, 510, 547-551.
http://dx.doi.org/10.1038/nature13267
[33]  De Vos, K., Goossens, V., Boone, E., Vercammen, D., Vancompernolle, K., Vandenabeele, P., Haegeman, G., Fiers, W. and Grooten, J. (1998) The 55-kDa Tumor Necrosis Factor Receptor Induces Clustering of Mitochondria through Its Membrane-Proximal Region. The Journal of Biological Chemistry, 273, 9673-9680.
http://dx.doi.org/10.1074/jbc.273.16.9673
[34]  Al-Mehdi, A.B., Pastukh, V.M., Swiger, B.M., Reed, D.J., Patel, M.R., Bardwell, G.C., Pastukh, V.V., Alexeyev, M.F. and Gillespie, M.N. (2012) Perinuclear Mitochondrial Clustering Creates an Oxidant-Rich Nuclear Domain Required for Hypoxia-Induced Transcription. Science Signaling, 5, ra47.
http://dx.doi.org/10.1126/scisignal.2002712
[35]  Bavister, B.D. (2006) The Mitochondrial Contribution to Stem Cell Biology. Reproduction, Fertility and Development, 18, 829-838.
http://dx.doi.org/10.1071/RD06111
[36]  Lonergan, T., Bavister, B. and Brenner, C. (2007) Mitochondria in Stem Cells. Mitochondrion, 7, 289-296.
http://dx.doi.org/10.1016/j.mito.2007.05.002

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