The MEF2-HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

Journal of Cell Science

Volumn 128, Issue 21, 2015, Pages 3961-3976

  Clocchiatti, Andrea ^a,c   Di Giorgio, Eros ^a   Viviani, Giulia ^a   Streuli, Charles ^b   Sgorbissa, Andrea ^a   Picco, Raffaella ^a   Cutano, Valentina ^a   Brancolini, Claudio ^a  

^a UNIVERSITY OF UDINE   (Italy)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

3D culture; Apoptosis; Breast cancer; CDKN1A; Cell cycle; ERBB2; H3K27; HDAC4; HDAC5; HDAC7; HER2; Lapatinib; MEF2A; MEF2D; Morphogenesis; P21

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1A; EPIDERMAL GROWTH FACTOR RECEPTOR 2; HISTONE DEACETYLASE; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE 5; HISTONE DEACETYLASE 7; HISTONE DEACETYLASE 9; MESSENGER RNA; MYOCYTE ENHANCER FACTOR 2; PROTEASOME;

ACINAR CELL; ACINI FORMATION; ARTICLE; AUTOPHAGY; BREAST EPITHELIUM CELL; CELL MATURATION; CELL PROLIFERATION; CELL SURVIVAL; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DOWN REGULATION; ENHANCER REGION; EPIGENETICS; EXPRESSED SEQUENCE TAG; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IN VITRO STUDY; INTRON; MORPHOGENESIS; NORMAL HUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; UPREGULATION; CELL LINE; CHROMATIN IMMUNOPRECIPITATION; EPITHELIUM CELL; FLUORESCENT ANTIBODY TECHNIQUE; GENETICS; IMMUNOBLOTTING; METABOLISM; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ACINAR CELLS; CELL LINE; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; EPITHELIAL CELLS; FLUORESCENT ANTIBODY TECHNIQUE; HISTONE DEACETYLASES; HUMANS; IMMUNOBLOTTING; MEF2 TRANSCRIPTION FACTORS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84946042122     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.170357     Document Type: Article

References (65)

1. Arnold, M. A., Kim, Y., Czubryt, M. P., Phan, D., McAnally, J., Qi, X., Shelton, J. M., Richardson, J. A., Bassel-Duby, R. and Olson, E. N. (2007). MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev. Cell 12, 377-389.
2. Besson, A., Dowdy, S. F. and Roberts, J. M. (2008). CDK inhibitors: cell cycle regulators and beyond. Dev. Cell 14, 159-169.
3. Cernotta, N., Clocchiatti, A., Florean, C. and Brancolini, C. (2011). Ubiquitindependent degradation of HDAC4, a new regulator of random cell motility. Mol. Biol. Cell 22, 278-289.
4. Clocchiatti, A., Florean, C. and Brancolini, C. (2011). Class IIa HDACs: from important roles in differentiation to possible implications in tumourigenesis. J. Cell. Mol. Med. 15, 1833-1846.
5. Clocchiatti, A., Di Giorgio, E., Demarchi, F. and Brancolini, C. (2013a). Beside the MEF2 axis: unconventional functions of HDAC4. Cell. Signal. 25, 269-276.
6. Clocchiatti, A., Di Giorgio, E., Ingrao, S., Meyer-Almes, F.-J., Tripodo, C. and Brancolini, C. (2013b). Class IIa HDACs repressive activities on MEF2-depedent transcription are associated with poor prognosis of ER(+) breast tumors. FASEB J. 27, 942-954.
7. Collette, N. M., Genetos, D. C., Economides, A. N., Xie, L., Shahnazari, M., Yao, W., Lane, N. E., Harland, R. M. and Loots, G. G. (2012). Targeted deletion of Sost distal enhancer increases bone formation and bone mass. Proc. Natl. Acad. Sci. USA 109, 14092-14097.
8. Curtis, C., Shah, S. P., Chin, S.-F., Turashvili, G., Rueda, O. M., Dunning, M. J., Speed, D., Lynch, A. G., Samarajiwa, S., Yuan, Y. et al. (2012). The genomic and transcriptomic architecture of 2, 000 breast tumours reveals novel subgroups. Nature 486, 346-352.
9. Debnath, J., Mills, K. R., Collins, N. L., Reginato, M. J., Muthuswamy, S. K. and Brugge, J. S. (2002). The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111, 29-40.
10. Debnath, J., Muthuswamy, S. K. and Brugge, J. S. (2003). Morphogenesis and oncogenesis of MCF10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30, 256-268.
11. Debnath, I., Roundy, K. M., Pioli, P. D., Weis, J. J. and Weis, J. H. (2013). Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins. Int. Immunol. 25, 99-115.
12. Demarchi, F., Bertoli, C., Copetti, T., Tanida, I., Brancolini, C., Eskelinen, E.-L. and Schneider, C. (2006). Calpain is required for macroautophagy in mammalian cells. J. Cell Biol. 175, 595-605.
13. Dequiedt, F., Kasler, H., Fischle, W., Kiermer, V., Weinstein, M., Herndier, B. G. and Verdin, E. (2003). HDAC7, a thymus-specific class II histone deacetylase, regulates Nur77 transcription and TCR-mediated apoptosis. Immunity 18, 687-698.
14. Di Giorgio, E., Clocchiatti, A., Piccinin, S., Sgorbissa, A., Viviani, G., Peruzzo, P., Romeo, S., Rossi, S., Dei Tos, A. P., Maestro, R. et al. (2013). MEF2 is a converging hub for histone deacetylase 4 and phosphatidylinositol 3-kinase/Aktinduced transformation. Mol. Cell. Biol. 33, 4473-4491.
15. Di Giorgio, E., Gagliostro, E. and Brancolini, C. (2015a). Selective class IIa HDAC inhibitors: myth or reality. Cell. Mol. Life Sci. 72, 73-86.
16. Di Giorgio, E., Gagliostro, E., Clocchiatti, A. and Brancolini, C. (2015b). The control operated by the cell cycle machinery on MEF2 stability contributes to the downregulation of CDKN1A and entry into S phase. Mol. Cell. Biol. 35, 1633-1647.
17. Dressel, U., Bailey, P. J., Wang, S.-C. M., Downes, M., Evans, R. M. and Muscat, G. E. O. (2001). A dynamic role for HDAC7 in MEF2-mediated muscle differentiation. J. Biol. Chem. 276, 17007-17013.
18. Elston, C. W. and Ellis, I. O. (2002). Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410. Histopathology 41, 151, discussion 152-153.
19. Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M. et al. (2011). Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43-49.
20. Flavell, S. W., Cowan, C. W., Kim, T.-K., Greer, P. L., Lin, Y., Paradis, S., Griffith, E. C., Hu, L. S., Chen, C. and Greenberg, M. E. (2006). Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311, 1008-1012.
21. Frisch, S. M., Schaller, M. and Cieply, B. (2013). Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J. Cell Sci. 126, 21-29.
22. Gjorevski, N. and Nelson, C. M. (2011). Integrated morphodynamic signalling of the mammary gland. Nat. Rev. Mol. Cell Biol. 12, 581-593.
23. Gregoire, S., Tremblay, A. M., Xiao, L., Yang, Q., Ma, K., Nie, J., Mao, Z., Wu, Z., Giguere, V. and Yang, X.-J. (2006). Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. J. Biol. Chem. 281, 4423-4433.
24. Haberland, M., Arnold, M. A., McAnally, J., Phan, D., Kim, Y. and Olson, E. N. (2007). Regulation of HDAC9 gene expression by MEF2 establishes a negativefeedback loop in the transcriptional circuitry of muscle differentiation. Mol. Cell. Biol. 27, 518-525.
25. Ishikawa, F., Miyoshi, H., Nose, K. and Shibanuma, M. (2010). Transcriptional induction of MMP-10 by TGF-beta, mediated by activation of MEF2A and downregulation of class IIa HDACs. Oncogene 29, 909-919.
26. Kramer, I., Baertschi, S., Halleux, C., Keller, H. and Kneissel, M. (2012). Mef2c deletion in osteocytes results in increased bone mass. J. Bone Miner. Res. 27, 360-373.
27. Lahm, A., Paolini, C., Pallaoro, M., Nardi, M. C., Jones, P., Neddermann, P., Sambucini, S., Bottomley, M. J., Lo Surdo, P., Carfi, A. et al. (2007). Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc. Natl. Acad. Sci. USA 104, 17335-17340.
28. Lee, J. L. and Streuli, C. H. (2014). Integrins and epithelial cell polarity. J. Cell Sci. 127, 3217-3225.
29. Leung, C. T. and Brugge, J. S. (2012). Outgrowth of single oncogene-expressing cells from suppressive epithelial environments. Nature 482, 410-413.
30. Lewandowski, K. T. and Piwnica-Worms, H. (2014). Phosphorylation of the E3 ubiquitin ligase RNF41 by the kinase Par-1b is required for epithelial cell polarity. J. Cell Sci. 127, 315-327.
31. Lin, Q., Schwarz, J., Bucana, C. and Olson, E. N. (1997). Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276, 1404-1407.
32. Lin, Q., Lu, J., Yanagisawa, H., Webb, R., Lyons, G. E., Richardson, J. A. and Olson, E. N. (1998). Requirement of the MADS-box transcription factor MEF2C for vascular development. Development 125, 4565-4574.
33. Liu, R., Wang, L., Chen, G., Katoh, H., Chen, C., Liu, Y. and Zheng, P. (2009). FOXP3 up-regulates p21 expression by site-specific inhibition of histone deacetylase 2/histone deacetylase 4 association to the locus. Cancer Res. 69, 2252-2259.
34. Liu, N., Nelson, B. R., Bezprozvannaya, S., Shelton, J. M., Richardson, J. A., Bassel-Duby, R. and Olson, E. N. (2014). Requirement of MEF2A, C, and D for skeletal muscle regeneration. Proc. Natl. Acad. Sci. USA 111, 4109-4114.
35. Lo, A. T., Mori, H., Mott, J. and Bissell, M. J. (2012). Constructing threedimensional models to study mammary gland branching morphogenesis and functional differentiation. J. Mammary Gland Biol. Neoplasia 17, 103-110.
36. Lu, J., McKinsey, T. A., Nicol, R. L. and Olson, E. N. (2000). Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases. Proc. Natl. Acad. Sci. USA 97, 4070-4075.
37. Ma, L., Liu, J., Liu, L., Duan, G., Wang, Q., Xu, Y., Xia, F., Shan, J., Shen, J., Yang, Z. et al. (2014). Overexpression of the transcription factor MEF2D in hepatocellular carcinoma sustains malignant character by suppressing G2-M transition genes. Cancer Res. 74, 1452-1462.
38. Mailleux, A. A., Overholtzer, M. and Brugge, J. S. (2008). Lumen formation during mammary epithelial morphogenesis: insights from in vitro and in vivo models. Cell Cycle 7, 57-62.
39. McKinsey, T. A., Zhang, C.-L., Lu, J. and Olson, E. N. (2000). Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 408, 106-111.
40. Mills, K. R., Reginato, M., Debnath, J., Queenan, B. and Brugge, J. S. (2004). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro. Proc. Natl. Acad. Sci. USA 101, 3438-3443.
41. Mottet, D., Pirotte, S., Lamour, V., Hagedorn, M., Javerzat, S., Bikfalvi, A., Bellahcene, A., Verdin, E. and Castronovo, V. (2009). HDAC4 represses p21 (WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene 28, 243-256.
42. Muthuswamy, S. K., Li, D., Lelievre, S., Bissell, M. J. and Brugge, J. S. (2001). ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini. Nat. Cell Biol. 3, 785-792.
43. Naya, F. J., Black, B. L., Wu, H., Bassel-Duby, R., Richardson, J. A., Hill, J. A. and Olson, E. N. (2002). Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat. Med. 8, 1303-1309.
44. Nebbioso, A., Manzo, F., Miceli, M., Conte, M., Manente, L., Baldi, A., De Luca, A., Rotili, D., Valente, S., Mai, A. et al. (2009). Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC-MEF2 complexes. EMBO Rep. 10, 776-782.
45. Pallavi, S. K., Ho, D. M., Hicks, C., Miele, L. and Artavanis-Tsakonas, S. (2012). Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila. EMBO J. 31, 2895-2907.
46. Paroni, G., Henderson, C., Schneider, C. and Brancolini, C. (2001). Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV-or tumor necrosis factor-dependent cell death requires caspase-3. J. Biol. Chem. 276, 21907-21915.
47. Paroni, G., Mizzau, M., Henderson, C., Del Sal, G., Schneider, C. and Brancolini, C. (2004). Caspase-dependent regulation of histone deacetylase 4 nuclearcytoplasmic shuttling promotes apoptosis. Mol. Biol. Cell 15, 2804-2818.
48. Paroni, G., Cernotta, N., Dello Russo, C., Gallinari, P., Pallaoro, M., Foti, C., Talamo, F., Orsatti, L., Steinkuhler, C. and Brancolini, C. (2008). PP2A regulates HDAC4 nuclear import. Mol. Biol. Cell 19, 655-667.
49. Potthoff, M. J. and Olson, E. N. (2007). MEF2: a central regulator of diverse developmental programs. Development 134, 4131-4140.
50. Potthoff, M. J., Wu, H., Arnold, M. A., Shelton, J. M., Backs, J., McAnally, J., Richardson, J. A., Bassel-Duby, R. and Olson, E. N. (2007). Histone deacetylase degradation and MEF2 activation promote the formation of slowtwitch myofibers. J. Clin. Invest. 117, 2459-2467.
51. Reginato, M. J., Mills, K. R., Paulus, J. K., Lynch, D. K., Sgroi, D. C., Debnath, J., Muthuswamy, S. K. and Brugge, J. S. (2003). Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat. Cell Biol. 5, 733-740.
52. Rosenbloom, K. R., Sloan, C. A., Malladi, V. S., Dreszer, T. R., Learned, K., Kirkup, V. M., Wong, M. C., Maddren, M., Fang, R., Heitner, S. G. et al. (2013). ENCODE data in the UCSC Genome Browser: year 5 update. Nucleic Acids Res. 41, D56-D63.
53. Saramaki, A., Diermeier, S., Kellner, R., Laitinen, H., Vaisanen, S. and Carlberg, C. (2009). Cyclical chromatin looping and transcription factor association on the regulatory regions of the p21 (CDKN1A) gene in response to 1alpha, 25-dihydroxyvitamin D3. J. Biol. Chem. 284, 8073-8082.
54. Schuetz, C. S., Bonin, M., Clare, S. E., Nieselt, K., Sotlar, K., Walter, M., Fehm, T., Solomayer, E., Riess, O., Wallwiener, D. et al. (2006). Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. Cancer Res. 66, 5278-5286.
55. Sebastian, S., Faralli, H., Yao, Z., Rakopoulos, P., Palii, C., Cao, Y., Singh, K., Liu, Q.-C., Chu, A., Aziz, A. et al. (2013). Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation. Genes Dev. 27, 1247-1259.
56. Shaw, K. R. M., Wrobel, C. N. and Brugge, J. S. (2004). Use of three-dimensional basement membrane cultures to model oncogene-induced changes in mammary epithelial morphogenesis. J. Mammary Gland Biol. Neoplasia 9, 297-310.
57. Simpson, D. R., Yu, M., Zheng, S., Zhao, Z., Muthuswamy, S. K. and Tansey, W. P. (2011). Epithelial cell organization suppresses Myc function by attenuating Myc expression. Cancer Res. 71, 3822-3830.
58. Streuli, C. H., Bailey, N. and Bissell, M. J. (1991). Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J. Cell Biol. 115, 1383-1395.
59. Wang, P., Valentijn, A. J., Gilmore, A. P. and Streuli, C. H. (2003). Early events in the anoikis program occur in the absence of caspase activation. J. Biol. Chem. 278, 19917-19925.
60. Weaver, V. M., Lelièvre, S., Lakins, J. N., Chrenek, M. A., Jones, J. C. R., Giancotti, F., Werb, Z. and Bissell, M. J. (2002). beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2, 205-216.
61. Whyte, J., Thornton, L., McNally, S., McCarthy, S., Lanigan, F., Gallagher, W. M., Stein, T. and Martin, F. (2010). PKCzeta regulates cell polarisation and proliferation restriction during mammary acinus formation. J. Cell Sci. 123, 3316-3328.
62. Wilson, A. J., Byun, D.-S., Nasser, S., Murray, L. B., Ayyanar, K., Arango, D., Figueroa, M., Melnick, A., Kao, G. D., Augenlicht, L. H. et al. (2008). HDAC4 promotes growth of colon cancer cells via repression of p21. Mol. Biol. Cell 19, 4062-4075.
63. Xia, W., Chen, J.-S., Zhou, X., Sun, P.-R., Lee, D.-F., Liao, Y., Zhou, B. P. and Hung, M.-C. (2004). Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients. Clin. Cancer Res. 10, 3815-3824.
64. Yang, X.-J. and Seto, E. (2008). The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat. Rev. Mol. Cell Biol. 9, 206-218.
65. Yu, M., Lin, G., Arshadi, N., Kalatskaya, I., Xue, B., Haider, S., Nguyen, F., Boutros, P. C., Elson, A., Muthuswamy, L. B. et al. (2012). Expression profiling during mammary epithelial cell three-dimensional morphogenesis identifies PTPRO as a novel regulator of morphogenesis and ErbB2-mediated transformation. Mol. Cell. Biol. 32, 3913-3924.