DOI QR코드

DOI QR Code

Emerging role of transient receptor potential (TRP) channels in cancer progression

  • Yang, Dongki (Department of Physiology, College of Medicine, Gachon University) ;
  • Kim, Jaehong (Department of Biochemistry, College of Medicine, Gachon University)
  • 투고 : 2020.01.14
  • 발행 : 2020.03.31

초록

Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca2+ distribution. The resulting dysregulation of multiple downstream effectors, depending on Ca2+ homeostasis, is associated with hallmarks of cancer pathophysiology, including enhanced proliferation, survival and invasion of cancer cells. These findings indicate that TRP channels affect multiple events that control cellular fate and play a key role in cancer progression. This review discusses the accumulating evidence supporting the role of TRP channels in tumorigenesis, with emphasis on prostate cancer.

키워드

참고문헌

  1. Costa-Pereira AP and Cotter TG (1999) Molecular and cellular biology of prostate cancer-the role of apoptosis as a target for therapy. Prostate Cancer Prostatic Dis 2, 126-139 https://doi.org/10.1038/sj/pcan/4500305
  2. Tapia-Vieyra JV and Mas-Oliva J (2001) Apoptosis and cell death channels in prostate cancer. Arch Med Res 32, 175-185 https://doi.org/10.1016/S0188-4409(01)00274-0
  3. Wertz IE and Dixit VM (2000) Characterization of calcium release-activated apoptosis of LNCaP prostate cancer cells. J Biol Chem 275, 11470-11477 https://doi.org/10.1074/jbc.275.15.11470
  4. Xue W, Zender L, Miething C et al (2007) Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660 https://doi.org/10.1038/nature05529
  5. Fels B, Bulk E, Petho Z and Schwab A (2018) The Role of TRP Channels in the Metastatic Cascade. Pharmaceuticals (Basel) 11, 48 https://doi.org/10.3390/ph11020048
  6. Berridge MJ, Lipp P and Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1, 11-21 https://doi.org/10.1038/35036035
  7. Clapham DE (1995) Calcium signaling. Cell 80, 259-268 https://doi.org/10.1016/0092-8674(95)90408-5
  8. Csordas G, Varnai P, Golenar T et al (2010) Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell 39, 121-132 https://doi.org/10.1016/j.molcel.2010.06.029
  9. Baudouin-Legros M, Brouillard F, Tondelier D, Hinzpeter A and Edelman A (2003) Effect of ouabain on CFTR gene expression in human Calu-3 cells. Am J Physiol Cell Physiol 284, C620-626 https://doi.org/10.1152/ajpcell.00457.2002
  10. McConkey DJ and Orrenius S (1997) The role of calcium in the regulation of apoptosis. Biochem Biophys Res Commun 239, 357-366 https://doi.org/10.1006/bbrc.1997.7409
  11. Parekh AB (2011) Decoding cytosolic Ca2+ oscillations. Trends Biochem Sci 36, 78-87 https://doi.org/10.1016/j.tibs.2010.07.013
  12. Berridge MJ (1997) The AM and FM of calcium signalling. Nature 386, 759-760 https://doi.org/10.1038/386759a0
  13. Smedler E and Uhlen P (2014) Frequency decoding of calcium oscillations. Biochim Biophys Acta 1840, 964-969 https://doi.org/10.1016/j.bbagen.2013.11.015
  14. Cullen PJ (2003) Calcium signalling: the ups and downs of protein kinase C. Curr Biol 13, R699-701 https://doi.org/10.1016/j.cub.2003.08.041
  15. Hu Q, Deshpande S, Irani K and Ziegelstein RC (1999) [Ca(2+)](i) oscillation frequency regulates agonist-stimulated NF-kappaB transcriptional activity. J Biol Chem 274, 33995-33998 https://doi.org/10.1074/jbc.274.48.33995
  16. Zeng X, Sikka SC, Huang L et al (2010) Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation. Prostate Cancer Prostatic Dis 13, 195-201 https://doi.org/10.1038/pcan.2009.55
  17. Bidaux G, Beck B, Zholos A et al (2012) Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms. J Biol Chem 287, 2948-2962 https://doi.org/10.1074/jbc.M111.270256
  18. Bidaux G, Borowiec AS, Gordienko D et al (2015) Epidermal TRPM8 channel isoform controls the balance between keratinocyte proliferation and differentiation in a cold-dependent manner. Proc Natl Acad Sci U S A 112, E3345-3354 https://doi.org/10.1073/pnas.1423357112
  19. Patapoutian A, Tate S and Woolf CJ (2009) Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov 8, 55-68 https://doi.org/10.1038/nrd2757
  20. Prevarskaya N, Zhang L and Barritt G (2007) TRP channels in cancer. Biochim Biophys Acta 1772, 937-946 https://doi.org/10.1016/j.bbadis.2007.05.006
  21. Gkika D and Prevarskaya N (2009) Molecular mechanisms of TRP regulation in tumor growth and metastasis. Biochim Biophys Acta 1793, 953-958 https://doi.org/10.1016/j.bbamcr.2008.11.010
  22. Santoni G, Farfariello V and Amantini C (2011) TRPV channels in tumor growth and progression. Adv Exp Med Biol 704, 947-967 https://doi.org/10.1007/978-94-007-0265-3_49
  23. Talmadge JE and Fidler IJ (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 70, 5649-5669 https://doi.org/10.1158/0008-5472.CAN-10-1040
  24. Hanahan D and Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674 https://doi.org/10.1016/j.cell.2011.02.013
  25. Cosens DJ and Manning A (1969) Abnormal electroretinogram from a Drosophila mutant. Nature 224, 285-287 https://doi.org/10.1038/224285a0
  26. Yoshida T, Inoue R, Morii T et al (2006) Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol 2, 596-607 https://doi.org/10.1038/nchembio821
  27. Rizza S and Filomeni G (2018) Role, targets and regulation of (de)nitrosylation in Malignancy. Front Oncol 8, 334 https://doi.org/10.3389/fonc.2018.00334
  28. Goel M, Sinkins WG and Schilling WP (2002) Selective association of TRPC channel subunits in rat brain synaptosomes. J Biol Chem 277, 48303-48310 https://doi.org/10.1074/jbc.M207882200
  29. Hofmann T, Schaefer M, Schultz G and Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci U S A 99, 7461-7466 https://doi.org/10.1073/pnas.102596199
  30. Schaefer M (2005) Homo- and heteromeric assembly of TRP channel subunits. Pflugers Arch 451, 35-42 https://doi.org/10.1007/s00424-005-1467-6
  31. Strubing C, Krapivinsky G, Krapivinsky L and Clapham DE (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 278, 39014-39019 https://doi.org/10.1074/jbc.M306705200
  32. Strubing C, Krapivinsky G, Krapivinsky L and Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29, 645-655 https://doi.org/10.1016/S0896-6273(01)00240-9
  33. Liu X, Bandyopadhyay BC, Singh BB, Groschner K and Ambudkar IS (2005) Molecular analysis of a storeoperated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel. Heteromeric assembly of TRPC1-TRPC3. J Biol Chem 280, 21600-21606 https://doi.org/10.1074/jbc.C400492200
  34. Gudermann T, Hofmann T, Mederos y Schnitzler M and Dietrich A (2004) Activation, subunit composition and physiological relevance of DAG-sensitive TRPC proteins. Novartis Found Symp 258, 103-118; discussion 118- 122, 155-159, 263-266
  35. Zagranichnaya TK, Wu X and Villereal ML (2005) Endogenous TRPC1, TRPC3, and TRPC7 proteins combine to form native store-operated channels in HEK-293 cells. J Biol Chem 280, 29559-29569 https://doi.org/10.1074/jbc.M505842200
  36. Poteser M, Graziani A, Rosker C et al (2006) TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3-TRPC4 heteromeric channels in endothelial cells. J Biol Chem 281, 13588-13595 https://doi.org/10.1074/jbc.M512205200
  37. Plant TD and Schaefer M (2003) TRPC4 and TRPC5: receptor-operated Ca2+-permeable nonselective cation channels. Cell Calcium 33, 441-450 https://doi.org/10.1016/S0143-4160(03)00055-1
  38. Plant TD and Schaefer M (2005) Receptor-operated cation channels formed by TRPC4 and TRPC5. Naunyn Schmiedebergs Arch Pharmacol 371, 266-276 https://doi.org/10.1007/s00210-005-1055-5
  39. Venkatachalam K, Hofmann T and Montell C (2006) Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. J Biol Chem 281, 17517-17527 https://doi.org/10.1074/jbc.M600807200
  40. Curcio-Morelli C, Zhang P, Venugopal B et al (2010) Functional multimerization of mucolipin channel proteins. J Cell Physiol 222, 328-335 https://doi.org/10.1002/jcp.21956
  41. Tsuruda PR, Julius D and Minor DL Jr (2006) Coiled coils direct assembly of a cold-activated TRP channel. Neuron 51, 201-212 https://doi.org/10.1016/j.neuron.2006.06.023
  42. Chubanov V, Mederos y Schnitzler M, Waring J, Plank A and Gudermann T (2005) Emerging roles of TRPM6/ TRPM7 channel kinase signal transduction complexes. Naunyn Schmiedebergs Arch Pharmacol 371, 334-341 https://doi.org/10.1007/s00210-005-1056-4
  43. Chubanov V, Waldegger S, Mederos y Schnitzler M et al (2004) Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. Proc Natl Acad Sci U S A 101, 2894-2899 https://doi.org/10.1073/pnas.0305252101
  44. Jiang LH (2007) Subunit interaction in channel assembly and functional regulation of transient receptor potential melastatin (TRPM) channels. Biochem Soc Trans 35, 86-88 https://doi.org/10.1042/BST0350086
  45. Li M, Jiang J and Yue L (2006) Functional characterization of homo- and heteromeric channel kinases TRPM6 and TRPM7. J Gen Physiol 127, 525-537 https://doi.org/10.1085/jgp.200609502
  46. Cheng W, Yang F, Takanishi CL and Zheng J (2007) Thermosensitive TRPV channel subunits coassemble into heteromeric channels with intermediate conductance and gating properties. J Gen Physiol 129, 191-207 https://doi.org/10.1085/jgp.200709731
  47. Hellwig N, Albrecht N, Harteneck C, Schultz G and Schaefer M (2005) Homo- and heteromeric assembly of TRPV channel subunits. J Cell Sci 118, 917-928 https://doi.org/10.1242/jcs.01675
  48. Liapi A and Wood JN (2005) Extensive co-localization and heteromultimer formation of the vanilloid receptorlike protein TRPV2 and the capsaicin receptor TRPV1 in the adult rat cerebral cortex. Eur J Neurosci 22, 825-834 https://doi.org/10.1111/j.1460-9568.2005.04270.x
  49. Smith GD, Gunthorpe MJ, Kelsell RE et al (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186-190 https://doi.org/10.1038/nature00894
  50. Garcia-Sanz N, Fernandez-Carvajal A, Morenilla-Palao C et al (2004) Identification of a tetramerization domain in the C terminus of the vanilloid receptor. J Neurosci 24, 5307-5314 https://doi.org/10.1523/JNEUROSCI.0202-04.2004
  51. Vlachova V, Teisinger J, Susankova K, Lyfenko A, Ettrich R and Vyklicky L (2003) Functional role of C-terminal cytoplasmic tail of rat vanilloid receptor 1. J Neurosci 23, 1340-1350 https://doi.org/10.1523/jneurosci.23-04-01340.2003
  52. Zhang F, Liu S, Yang F, Zheng J and Wang K (2011) Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels. J Biol Chem 286, 15308-15316 https://doi.org/10.1074/jbc.M111.223941
  53. Kopanska KS, Alcheikh Y, Staneva R, Vignjevic D and Betz T (2016) Tensile forces originating from cancer spheroids facilitate tumor invasion. PLoS One 11, e0156442 https://doi.org/10.1371/journal.pone.0156442
  54. Wei SC and Yang J (2016) Forcing through Tumor Metastasis: The Interplay between tissue rigidity and epithelial-mesenchymal transition. Trends Cell Biol 26, 111-120 https://doi.org/10.1016/j.tcb.2015.09.009
  55. Broders-Bondon F, Nguyen Ho-Bouldoires TH, Fernandez-Sanchez ME and Farge E (2018) Mechanotransduction in tumor progression: The dark side of the force. J Cell Biol 217, 1571-1587 https://doi.org/10.1083/jcb.201701039
  56. Chubanov V, Mittermeier L and Gudermann T (2018) Role of kinase-coupled TRP channels in mineral homeostasis. Pharmacol Ther 184, 159-176 https://doi.org/10.1016/j.pharmthera.2017.11.003
  57. Schilling T, Miralles F and Eder C (2014) TRPM7 regulates proliferation and polarisation of macrophages. J Cell Sci 127, 4561-4566 https://doi.org/10.1242/jcs.151068
  58. Clark K, Langeslag M, van Leeuwen B et al (2006) TRPM7, a novel regulator of actomyosin contractility and cell adhesion. EMBO J 25, 290-301 https://doi.org/10.1038/sj.emboj.7600931
  59. Nishitani WS, Alencar AM and Wang Y (2015) Rapid and localized mechanical stimulation and adhesion assay: TRPM7 involvement in calcium signaling and cell adhesion. PLoS One 10, e0126440 https://doi.org/10.1371/journal.pone.0126440
  60. Gao SL, Kong CZ, Zhang Z, Li ZL, Bi JB and Liu XK (2017) TRPM7 is overexpressed in bladder cancer and promotes proliferation, migration, invasion and tumor growth. Oncol Rep 38, 1967-1976 https://doi.org/10.3892/or.2017.5883
  61. Middelbeek J, Kuipers AJ, Henneman L et al (2012) TRPM7 is required for breast tumor cell metastasis. Cancer Res 72, 4250-4261 https://doi.org/10.1158/0008-5472.CAN-11-3863
  62. Wei C, Wang X, Chen M, Ouyang K, Song LS and Cheng H (2009) Calcium flickers steer cell migration. Nature 457, 901-905 https://doi.org/10.1038/nature07577
  63. Su LT, Agapito MA, Li M et al (2006) TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain. J Biol Chem 281, 11260-11270 https://doi.org/10.1074/jbc.M512885200
  64. Guilbert A, Gautier M, Dhennin-Duthille I et al (2013) Transient receptor potential melastatin 7 is involved in oestrogen receptor-negative metastatic breast cancer cells migration through its kinase domain. Eur J Cancer 49, 3694-3707 https://doi.org/10.1016/j.ejca.2013.07.008
  65. Meng X, Cai C, Wu J et al (2013) TRPM7 mediates breast cancer cell migration and invasion through the MAPK pathway. Cancer Lett 333, 96-102 https://doi.org/10.1016/j.canlet.2013.01.031
  66. Clark K, Middelbeek J, Lasonder E et al (2008) TRPM7 regulates myosin IIA filament stability and protein localization by heavy chain phosphorylation. J Mol Biol 378, 790-803 https://doi.org/10.1016/j.jmb.2008.02.057
  67. Chen JP, Wang J, Luan Y et al (2015) TRPM7 promotes the metastatic process in human nasopharyngeal carcinoma. Cancer Lett 356, 483-490 https://doi.org/10.1016/j.canlet.2014.09.032
  68. Chen JP, Luan Y, You CX, Chen XH, Luo RC and Li R (2010) TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2+) influx. Cell Calcium 47, 425-432 https://doi.org/10.1016/j.ceca.2010.03.003
  69. Yee NS, Kazi AA, Li Q, Yang Z, Berg A and Yee RK (2015) Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis. Biol Open 4, 507-514 https://doi.org/10.1242/bio.20137088
  70. Rybarczyk P, Vanlaeys A, Brassart B et al (2017) The transient receptor potential melastatin 7 channel regulates pancreatic cancer cell invasion through the Hsp90alpha/uPA/MMP2 pathway. Neoplasia 19, 288-300 https://doi.org/10.1016/j.neo.2017.01.004
  71. Yee NS, Chan AS, Yee JD and Yee RK (2012) TRPM7 and TRPM8 ion channels in pancreatic adenocarcinoma: potential roles as cancer biomarkers and targets. Scientifica (Cairo) 2012, 415158 https://doi.org/10.6064/2012/415158
  72. Wang J, Liao QJ, Zhang Y et al (2014) TRPM7 is required for ovarian cancer cell growth, migration and invasion. Biochem Biophys Res Commun 454, 547-553 https://doi.org/10.1016/j.bbrc.2014.10.118
  73. Dhennin-Duthille I, Gautier M, Faouzi M et al (2011) High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues: correlation with pathological parameters. Cell Physiol Biochem 28, 813-822 https://doi.org/10.1159/000335795
  74. Jiang J, Li MH, Inoue K, Chu XP, Seeds J and Xiong ZG (2007) Transient receptor potential melastatin 7-like current in human head and neck carcinoma cells: role in cell proliferation. Cancer Res 67, 10929-10938 https://doi.org/10.1158/0008-5472.CAN-07-1121
  75. Yee NS, Zhou W and Liang IC (2011) Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer. Dis Model Mech 4, 240-254 https://doi.org/10.1242/dmm.004564
  76. Caceres M, Ortiz L, Recabarren T et al (2015) TRPM4 Is a novel component of the adhesome required for focal adhesion disassembly, migration and contractility. PLoS One 10, e0130540 https://doi.org/10.1371/journal.pone.0130540
  77. Almasi S, Sterea AM, Fernando W et al (2019) TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway. Sci Rep 9, 4182 https://doi.org/10.1038/s41598-019-40330-1
  78. Lee WH, Choong LY, Mon NN et al (2016) TRPV4 regulates breast cancer cell extravasation, stiffness and actin cortex. Sci Rep 6, 27903 https://doi.org/10.1038/srep27903
  79. Lee WH, Choong LY, Jin TH et al (2017) TRPV4 plays a role in breast cancer cell migration via Ca(2+)- dependent activation of AKT and downregulation of E-cadherin cell cortex protein. Oncogenesis 6, e338 https://doi.org/10.1038/oncsis.2017.39
  80. Xie R, Xu J, Xiao Y et al (2017) Calcium promotes human gastric cancer via a novel coupling of calcium-sensing receptor and TRPV4 channel. Cancer Res 77, 6499-6512 https://doi.org/10.1158/0008-5472.CAN-17-0360
  81. Waning J, Vriens J, Owsianik G et al (2007) A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration. Cell Calcium 42, 17-25 https://doi.org/10.1016/j.ceca.2006.11.005
  82. Sahai E (2007) Illuminating the metastatic process. Nat Rev Cancer 7, 737-749 https://doi.org/10.1038/nrc2229
  83. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D (2011) Global cancer statistics. CA Cancer J Clin 61, 69-90 https://doi.org/10.3322/caac.20107
  84. Siegel RL, Miller KD and Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68, 7-30 https://doi.org/10.3322/caac.21442
  85. Gkika D and Prevarskaya N (2011) TRP channels in prostate cancer: the good, the bad and the ugly? Asian J Androl 13, 673-676 https://doi.org/10.1038/aja.2011.18
  86. Prevarskaya N, Flourakis M, Bidaux G, Thebault S and Skryma R (2007) Differential role of TRP channels in prostate cancer. Biochem Soc Trans 35, 133-135 https://doi.org/10.1042/BST0350133
  87. Van Haute C, De Ridder D and Nilius B (2010) TRP channels in human prostate. Scientific World Journal 10, 1597-1611 https://doi.org/10.1100/tsw.2010.149
  88. Flourakis M and Prevarskaya N (2009) Insights into Ca2+ homeostasis of advanced prostate cancer cells. Biochim Biophys Acta 1793, 1105-1109 https://doi.org/10.1016/j.bbamcr.2009.01.009
  89. Prevarskaya N, Skryma R and Shuba Y (2011) Calcium in tumour metastasis: new roles for known actors. Nat Rev Cancer 11, 609-618 https://doi.org/10.1038/nrc3105
  90. Skryma R, Prevarskaya N, Gkika D and Shuba Y (2011) From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. Nat Rev Urol 8, 617-630 https://doi.org/10.1038/nrurol.2011.142
  91. Gkika D, Lemonnier L, Shapovalov G et al (2015) TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity. J Cell Biol 208, 89-107 https://doi.org/10.1083/jcb.201402076
  92. Holzmann C, Kappel S, Kilch T et al (2015) Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells. Oncotarget 6, 41783-41793 https://doi.org/10.18632/oncotarget.6157
  93. Hong X and Yu JJ (2019) MicroRNA-150 suppresses epithelial-mesenchymal transition, invasion, and metastasis in prostate cancer through the TRPM4-mediated betacatenin signaling pathway. Am J Physiol Cell Physiol 316, C463-C480 https://doi.org/10.1152/ajpcell.00142.2018
  94. Sagredo AI, Sagredo EA, Pola V et al (2019) TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines. J Cell Physiol 234, 2037-2050 https://doi.org/10.1002/jcp.27371
  95. Hantute-Ghesquier A, Haustrate A, Prevarskaya N and Lehen'kyi V (2018) TRPM family channels in cancer. Pharmaceuticals (Basel) 11, 58 https://doi.org/10.3390/ph11020058
  96. Schinke EN, Bii V, Nalla A et al (2014) A novel approach to identify driver genes involved in androgenindependent prostate cancer. Mol Cancer 13, 120 https://doi.org/10.1186/1476-4598-13-120
  97. Chen L, Cao R, Wang G et al (2017) Downregulation of TRPM7 suppressed migration and invasion by regulating epithelial-mesenchymal transition in prostate cancer cells. Med Oncol 34, 127 https://doi.org/10.1007/s12032-017-0987-1
  98. Czifra G, Varga A, Nyeste K et al (2009) Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol 135, 507-514 https://doi.org/10.1007/s00432-008-0482-3
  99. Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N and Diaz-Laviada I (2006) Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 11, 89-99 https://doi.org/10.1007/s10495-005-3275-z
  100. Malagarie-Cazenave S, Olea-Herrero N, Vara D and Diaz-Laviada I (2009) Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3K and MAPK pathways in prostate LNCaP cells. FEBS Lett 583, 141-147 https://doi.org/10.1016/j.febslet.2008.11.038
  101. Monet M, Lehen'kyi V, Gackiere F et al (2010) Role of cationic channel TRPV2 in promoting prostate cancer migration and progression to androgen resistance. Cancer Res 70, 1225-1235 https://doi.org/10.1158/0008-5472.CAN-09-2205