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Djari C, Sahut-Barnola I, Septier A, et al. Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex. J Clin Invest. 2021;131(23)doi: 10.1172/JCI146910.
Djari, C., Sahut-Barnola, I., Septier, A., Plotton, I., Montanier, N., Dufour, D., Levasseur, A., Wilmouth, J., Pointud, J. C., Faucz, F. R., Kamilaris, C., Lopez, A. G., Guillou, F., Swain, A., Vainio, S. J., Tauveron, I., Val, P., Lefebvre, H., Stratakis, C. A., Martinez, A., & Lefrançois-Martinez, A. M. (2021). Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex. The Journal of clinical investigation, 131(23), . https://doi.org/10.1172/JCI146910
Djari, Cyril, et al. "Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex." The Journal of clinical investigation vol. 131,23 (2021). doi: https://doi.org/10.1172/JCI146910
Djari C, Sahut-Barnola I, Septier A, Plotton I, Montanier N, Dufour D, Levasseur A, Wilmouth J, Pointud JC, Faucz FR, Kamilaris C, Lopez AG, Guillou F, Swain A, Vainio SJ, Tauveron I, Val P, Lefebvre H, Stratakis CA, Martinez A, Lefrançois-Martinez AM. Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex. J Clin Invest. 2021 Dec 01;131(23). doi: 10.1172/JCI146910. PMID: 34850745; PMCID: PMC8631603.
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J Clin Invest. 2021 Dec 01;131(23). doi: 10.1172/JCI146910.

Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.

The Journal of clinical investigation

Cyril Djari, Isabelle Sahut-Barnola, Amandine Septier, Ingrid Plotton, Nathanaëlle Montanier, Damien Dufour, Adrien Levasseur, James Wilmouth, Jean-Christophe Pointud, Fabio R Faucz, Crystal Kamilaris, Antoine-Guy Lopez, Florian Guillou, Amanda Swain, Seppo J Vainio, Igor Tauveron, Pierre Val, Hervé Lefebvre, Constantine A Stratakis, Antoine Martinez, Anne-Marie Lefrançois-Martinez

Affiliations

  1. iGReD, Université Clermont-Auvergne, CNRS6293, INSERM U1103, Clermont-Ferrand, France.
  2. UM Pathologies Endocriniennes Rénales Musculaires et Mucoviscidose, Hospices Civils de Lyon, Bron, France.
  3. Université Clermont-Auvergne, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  4. Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland, USA.
  5. Normandie University, UNIROUEN, INSERM U1239, Rouen University Hospital, Department of Endocrinology, Diabetology and Metabolic Diseases and CIC-CRB 140h4, Rouen, France.
  6. PRC, INRAE, CNRS, IFCE, Tours University, Nouzilly, France.
  7. Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom.
  8. Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.

PMID: 34850745 PMCID: PMC8631603 DOI: 10.1172/JCI146910

Abstract

Large-cell calcifying Sertoli cell tumors (LCCSCTs) are among the most frequent lesions occurring in male Carney complex (CNC) patients. Although they constitute a key diagnostic criterion for this rare multiple neoplasia syndrome resulting from inactivating mutations of the tumor suppressor PRKAR1A, leading to unrepressed PKA activity, LCCSCT pathogenesis and origin remain elusive. Mouse models targeting Prkar1a inactivation in all somatic populations or separately in each cell type were generated to decipher the molecular and paracrine networks involved in the induction of CNC testis lesions. We demonstrate that the Prkar1a mutation was required in both stromal and Sertoli cells for the occurrence of LCCSCTs. Integrative analyses comparing transcriptomic, immunohistological data and phenotype of mutant mouse combinations led to the understanding of human LCCSCT pathogenesis and demonstrated PKA-induced paracrine molecular circuits in which the aberrant WNT4 signal production is a limiting step in shaping intratubular lesions and tumor expansion both in a mouse model and in human CNC testes.

Keywords: Endocrinology; Genetic diseases; Mouse models; Protein kinases; Reproductive Biology

References

  1. Endocr Rev. 2018 Oct 1;39(5):739-759 - PubMed
  2. Dev Biol. 2012 Apr 1;364(1):11-21 - PubMed
  3. Biol Reprod. 2016 Jul;95(1):13 - PubMed
  4. FASEB J. 2010 Aug;24(8):3010-25 - PubMed
  5. Biol Reprod. 2010 Jan;82(1):54-65 - PubMed
  6. Genesis. 2009 Nov;47(11):782-8 - PubMed
  7. Cancer Res. 2004 Dec 15;64(24):8811-5 - PubMed
  8. EMBO J. 2015 Mar 4;34(5):641-52 - PubMed
  9. Int Rev Cell Mol Biol. 2013;301:291-358 - PubMed
  10. Eur J Endocrinol. 1998 May;138(5):473-81 - PubMed
  11. J Endocrinol. 2006 Aug;190(2):351-61 - PubMed
  12. Mol Endocrinol. 2014 Sep;28(9):1471-86 - PubMed
  13. Andrology. 2018 Jan;6(1):3-9 - PubMed
  14. Hum Pathol. 2017 Jul;65:1-14 - PubMed
  15. Am J Surg Pathol. 2007 Jun;31(6):827-35 - PubMed
  16. Hum Reprod. 2006 Sep;21(9):2340-5 - PubMed
  17. J Clin Endocrinol Metab. 1996 Apr;81(4):1367-70 - PubMed
  18. Am J Surg Pathol. 2014 Jan;38(1):66-71 - PubMed
  19. Mech Dev. 2002 Apr;113(1):29-39 - PubMed
  20. J Biol Chem. 2001 Oct 26;276(43):40225-33 - PubMed
  21. Biol Reprod. 2010 Feb;82(2):422-32 - PubMed
  22. Physiology (Bethesda). 2010 Apr;25(2):85-101 - PubMed
  23. Am J Surg Pathol. 1997 Nov;21(11):1271-80 - PubMed
  24. Blood. 2004 Jul 1;104(1):51-7 - PubMed
  25. Development. 2009 Jun;136(11):1813-21 - PubMed
  26. Andrologia. 2007 Oct;39(5):196-7 - PubMed
  27. Dev Biol. 1993 Jan;155(1):68-74 - PubMed
  28. Cell Rep. 2014 Aug 7;8(3):723-33 - PubMed
  29. Nat Commun. 2019 Jan 2;10(1):6 - PubMed
  30. Curr Opin Oncol. 2007 Jan;19(1):24-9 - PubMed
  31. Mol Cell Endocrinol. 2006 Jun 27;252(1-2):126-35 - PubMed
  32. Mol Endocrinol. 2002 Nov;16(11):2582-91 - PubMed
  33. Front Endocrinol (Lausanne). 2018 Dec 14;9:763 - PubMed
  34. J Urol. 2002 Mar;167(3):1299-302 - PubMed
  35. Development. 2012 Dec;139(24):4561-70 - PubMed
  36. Nature. 1999 Feb 4;397(6718):405-9 - PubMed
  37. Endocrinology. 1999 Mar;140(3):1499-504 - PubMed
  38. Development. 2021 Jan 13;148(1): - PubMed
  39. Mol Cell Biol. 2005 Oct;25(20):9063-72 - PubMed
  40. Endocrinology. 2009 Nov;150(11):5036-45 - PubMed
  41. Curr Opin Pediatr. 2012 Aug;24(4):518-22 - PubMed
  42. Pathol Int. 2005 Jun;55(6):366-71 - PubMed
  43. Hum Pathol. 2017 Mar;61:181-189 - PubMed
  44. Mol Endocrinol. 1999 Jun;13(6):851-65 - PubMed
  45. Hum Mol Genet. 2014 Oct 15;23(20):5418-28 - PubMed
  46. Endocrinology. 2002 Jun;143(6):2259-67 - PubMed
  47. PLoS One. 2012;7(6):e37366 - PubMed
  48. J Cell Mol Med. 2020 Jun;24(12):7023-7033 - PubMed
  49. Cancer Res. 2005 Jun 1;65(11):4506-14 - PubMed
  50. PLoS One. 2012;7(1):e29764 - PubMed
  51. Hum Mol Genet. 2012 Oct 15;21(20):4394-405 - PubMed
  52. APMIS. 1998 Jan;106(1):101-12; discussion 112-3 - PubMed
  53. PLoS Genet. 2010 Jun 10;6(6):e1000980 - PubMed
  54. Mol Med Rep. 2016 Mar;13(3):2431-8 - PubMed
  55. Ann N Y Acad Sci. 2002 Jun;968:75-95 - PubMed
  56. Cell Signal. 2016 May;28(5):498-505 - PubMed
  57. Nat Commun. 2016 Sep 14;7:12751 - PubMed
  58. Mol Endocrinol. 2003 Apr;17(4):507-19 - PubMed
  59. PLoS One. 2011;6(10):e25585 - PubMed
  60. Int J Mol Sci. 2020 Jun 16;21(12): - PubMed
  61. Endocrinology. 2013 Oct;154(10):3900-13 - PubMed
  62. Biol Reprod. 2003 Dec;69(6):1979-88 - PubMed
  63. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12435-40 - PubMed
  64. Rev Endocr Metab Disord. 2011 Dec;12(4):303-21 - PubMed
  65. Dev Biol. 2006 Dec 15;300(2):545-53 - PubMed
  66. Cold Spring Harb Perspect Biol. 2016 Jul 01;8(7): - PubMed
  67. Biol Reprod. 2009 Nov;81(5):842-9 - PubMed
  68. Genesis. 2006 Sep;44(9):419-24 - PubMed
  69. Oncogenesis. 2017 Jul 24;6(7):e364 - PubMed
  70. Mol Endocrinol. 2013 May;27(5):814-27 - PubMed
  71. Genesis. 2002 Jul;33(3):114-8 - PubMed
  72. Arch Med Res. 1999 Nov-Dec;30(6):501-9 - PubMed
  73. J Endocrinol. 2020 Jan 1;244(3):R33-R46 - PubMed
  74. Development. 2000 May;127(10):2125-31 - PubMed
  75. Mol Cell Endocrinol. 2014 Mar 25;384(1-2):32-42 - PubMed
  76. Eur J Endocrinol. 2015 Oct;173(4):M85-97 - PubMed
  77. Histopathology. 2017 Mar;70(4):513-521 - PubMed
  78. Mol Endocrinol. 2006 Oct;20(10):2504-13 - PubMed
  79. Am J Physiol Endocrinol Metab. 2012 Oct 1;303(7):E886-98 - PubMed
  80. Mol Endocrinol. 2002 Mar;16(3):630-9 - PubMed
  81. J Clin Endocrinol Metab. 2001 Sep;86(9):4041-6 - PubMed
  82. Endocrinology. 1992 Dec;131(6):2928-34 - PubMed
  83. Front Endocrinol (Lausanne). 2019 Apr 16;10:224 - PubMed
  84. Genes Immun. 2010 Dec;11(8):599-608 - PubMed
  85. Cells. 2019 Aug 09;8(8): - PubMed
  86. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16934-8 - PubMed
  87. Endocr Rev. 2015 Oct;36(5):564-91 - PubMed
  88. J Cell Commun Signal. 2017 Dec;11(4):297-307 - PubMed
  89. Hum Mol Genet. 2009 Feb 1;18(3):405-17 - PubMed
  90. Biol Reprod. 2006 Jan;74(1):195-201 - PubMed
  91. PLoS One. 2010 Nov 30;5(11):e14168 - PubMed
  92. Nat Commun. 2012 Mar 13;3:735 - PubMed
  93. Reprod Sci. 2013 Mar;20(3):211-33 - PubMed
  94. Dev Biol. 2017 Jun 1;426(1):17-27 - PubMed
  95. J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91 - PubMed
  96. Medicine (Baltimore). 1985 Jul;64(4):270-83 - PubMed
  97. Science. 2018 Jun 29;360(6396):1469-1473 - PubMed

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