TRPM8: a potential target for cancer treatment

Liu, Zhaoguo; Wu, Hongyan; Wei, Zhonghong; Wang, Xu; Shen, Peiliang; Wang, Siliang; Wang, Aiyun; Chen, Wenxing; Lu, Yin

doi:10.1007/s00432-015-2112-1

Review – Cancer Research
Published: 23 January 2016

TRPM8: a potential target for cancer treatment

Zhaoguo Liu¹,
Hongyan Wu^1,2,
Zhonghong Wei¹,
Xu Wang¹,
Peiliang Shen¹,
Siliang Wang¹,
Aiyun Wang¹,
Wenxing Chen¹ &
Yin Lu^1,3

Journal of Cancer Research and Clinical Oncology volume 142, pages 1871–1881 (2016)Cite this article

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Abstract

Transient receptor potential (TRP) cation channel superfamily plays critical roles in variety of processes, including temperature perception, pain transduction, vasorelaxation, male fertility, and tumorigenesis. One of seven families within the TRP superfamily of ion channels, the melastatin, or TRPM family comprises a group of eight structurally and functionally diverse channels. Of all the members of TRPM subfamily, TRPM8 is the most notable one. A lot of literatures have demonstrated that transient receptor potential melastatin 8 (TRPM8) could perform a myriad of functions in vertebrates and invertebrates alike. In addition to its well-known function in cold sensation, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Recent studies have shown that TRPM8 is necessary to the initiation and progression of tumors, and the aberrant expression of TRPM8 was found in varieties of tumors, such as prostate tumor, melanoma, breast adenocarcinoma, bladder cancer, and colorectal cancer, making it a novel molecular target potentially useful in the diagnosis and treatment of cancer. This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy.

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References

Abed E, Labelle D, Martineau C, Loghin A, Moreau R (2009) Expression of transient receptor potential (TRP) channels in human and murine osteoblast-like cells. Mol Membr Biol 26:146–158. doi:10.1080/09687680802612721
CAS PubMed Article Google Scholar
Akiba S, Sato T (2004) Cellular function of calcium-independent phospholipase A2. Biol Pharm Bull 27:1174–1178
CAS PubMed Article Google Scholar
Alvarez JV, Pan TC, Ruth J, Feng Y, Zhou A, Pant D, Grimley JS, Wandless TJ, Demichele A, Chodosh LA (2013) Par-4 downregulation promotes breast cancer recurrence by preventing multinucleation following targeted therapy. Cancer Cell 24:30–44. doi:10.1016/j.ccr.2013.05.007
CAS PubMed Article Google Scholar
Andersson DA, Nash M, Bevan S (2007) Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids. J Neurosci 27:3347–3355. doi:10.1523/JNEUROSCI.4846-06.2007
CAS PubMed PubMed Central Article Google Scholar
Andrews MD, Af Forselles K, Beaumont K, Galan SR, Glossop PA, Grenie M, Jessiman A, Kenyon AS, Lunn G, Maw G, Owen RM, Pryde DC, Roberts D, Tran TD (2015) Discovery of a selective TRPM8 antagonist with clinical efficacy in cold-related pain. ACS Med Chem Lett 6:419–424. doi:10.1021/ml500479v
CAS PubMed PubMed Central Article Google Scholar
Anzalone CL, Cohen PR, Migden MR, Tannir NM (2013) Mohs surgery in metastatic cancer: renal cell carcinoma solitary cutaneous metastasis and visceral tumor metastases to skin treated with microscopically controlled surgical excision. Int J Dermatol 52:856–861. doi:10.1111/ijd.12021
PubMed Article Google Scholar
Asuthkar S, Velpula KK, Elustondo PA, Demirkhanyan L, Zakharian E (2015) TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells. Oncotarget 6:17221–17236
PubMed PubMed Central Article Google Scholar
Augustinakova A, Kodet R (2011) Gastrointestinal stromal tumor molecular diagnostics in relation to the prediction of a therapeutic response to targeted biological therapy. Ceskoslov Patol 47:148–152
CAS Google Scholar
Bai VU, Murthy S, Chinnakannu K, Muhletaler F, Tejwani S, Barrack ER, Kim SH, Menon M, Veer Reddy GP (2010) Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids. Int J Oncol 36:443–450
CAS PubMed Google Scholar
Bao P, Zhao W, Li Y, Liu Y, Zhou Y, Liu C (2015) Protective effect of ulinastatin in patients with non-small cell lung cancer after radiation therapy: a randomized, placebo-controlled study. Med Oncol 32:405. doi:10.1007/s12032-014-0405-x
PubMed Article CAS Google Scholar
Bates DO, Catalano PJ, Symonds KE, Varey AH, Ramani P, O’Dwyer PJ, Giantonio BJ, Meropol NJ, Benson AB, Harper SJ (2012) Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab. Clin Cancer Res 18:6384–6391. doi:10.1158/1078-0432.CCR-12-2223
CAS PubMed PubMed Central Article Google Scholar
Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004) Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 141:737–745. doi:10.1038/sj.bjp.0705652
CAS PubMed PubMed Central Article Google Scholar
Bodding M (2007) TRP proteins and cancer. Cell Signal 19:617–624. doi:10.1016/j.cellsig.2006.08.012
PubMed Article CAS Google Scholar
Bodding M, Wissenbach U, Flockerzi V (2007) Characterisation of TRPM8 as a pharmacophore receptor. Cell Calcium 42:618–628. doi:10.1016/j.ceca.2007.03.005
Borrelli F, Pagano E, Romano B, Panzera S, Maiello F, Coppola D, De Petrocellis L, Buono L, Orlando P, Izzo AA (2014) Colon carcinogenesis is inhibited by the TRPM8 antagonist cannabigerol, a Cannabis-derived non-psychotropic cannabinoid. Carcinogenesis 35:2787–2797. doi:10.1093/carcin/bgu205
CAS PubMed Article Google Scholar
Chen W, Lu Y, Wu J, Gao M, Wang A, Xu B (2011a) Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis. Cancer Chemother Pharmacol 67:799–808. doi:10.1007/s00280-010-1378-x
CAS PubMed Article Google Scholar
Chen ZJ, Roberts K, Decker R, Pathare P, Rockwell S, Nath R (2011b) The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers. Phys Med Biol 56:4895–4912. doi:10.1088/0031-9155/56/15/016
PubMed Article Google Scholar
Chodon D, Guilbert A, Dhennin-Duthille I, Gautier M, Telliez MS, Sevestre H, Ouadid-Ahidouch H (2010) Estrogen regulation of TRPM8 expression in breast cancer cells. BMC Cancer 10:212. doi:10.1186/1471-2407-10-212
PubMed PubMed Central Article CAS Google Scholar
Clapham DE (2007) SnapShot: mammalian TRP channels. Cell 129:220. doi:10.1016/j.cell.2007.03.034
PubMed Article Google Scholar
Clapham DE, Julius D, Montell C, Schultz G (2005) International Union of Pharmacology. XLIX. Nomenclature and structure–function relationships of transient receptor potential channels. Pharmacol Rev 57:427–450. doi:10.1124/pr.57.4.6
CAS PubMed Article Google Scholar
Cosens DJ, Manning A (1969) Abnormal electroretinogram from a Drosophila mutant. Nature 224:285–287
CAS PubMed Article Google Scholar
DeFalco J, Duncton MA, Emerling D (2011) TRPM8 biology and medicinal chemistry. Curr Top Med Chem 11:2237–2252
CAS PubMed Article Google Scholar
Du GJ, Li JH, Liu WJ, Liu YH, Zhao B, Li HR, Hou XD, Li H, Qi XX, Duan YJ (2014) The combination of TRPM8 and TRPA1 expression causes an invasive phenotype in lung cancer. Tumour Biol 35:1251–1261. doi:10.1007/s13277-013-1167-3
CAS PubMed Article Google Scholar
Emmenegger U, Kerbel RS (2010) Cancer: chemotherapy counteracted. Nature 468:637–638. doi:10.1038/468637a
CAS PubMed Article Google Scholar
Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 1:34–45. doi:10.1038/35094009
CAS PubMed Article Google Scholar
Fiorio Pla A, Gkika D (2013) Emerging role of TRP channels in cell migration: from tumor vascularization to metastasis. Front Physiol 4:311. doi:10.3389/fphys.2013.00311
PubMed PubMed Central Article Google Scholar
Fixemer T, Wissenbach U, Flockerzi V, Bonkhoff H (2003) Expression of the Ca²⁺-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. Oncogene 22:7858–7861. doi:10.1038/sj.onc.1206895
CAS PubMed Article Google Scholar
Fujita F, Uchida K, Takaishi M, Sokabe T, Tominaga M (2013) Ambient temperature affects the temperature threshold for TRPM8 activation through interaction of phosphatidylinositol 4,5-bisphosphate. J Neurosci 33:6154–6159. doi:10.1523/JNEUROSCI.5672-12.2013
CAS PubMed Article Google Scholar
Gardiner JC, Kirkup AJ, Curry J, Humphreys S, O'Regan P, Postlethwaite M, Young KC, Kitching L, Ethell BT, Winpenny D, McMurray G (2014) The role of TRPM8 in the Guinea-pig bladder-cooling reflex investigated using a novel TRPM8 antagonist. Eur J Pharmacol 740:398–409. doi:10.1016/j.ejphar.2014.07.022
CAS PubMed Article Google Scholar
Gauchan P, Andoh T, Kato A, Kuraishi Y (2009) Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice. Neurosci Lett 458:93–95. doi:10.1016/j.neulet.2009.04.029
CAS PubMed Article Google Scholar
Gkika D, Prevarskaya N (2009) Molecular mechanisms of TRP regulation in tumor growth and metastasis. Biochim Biophys Acta 1793:953–958. doi:10.1016/j.bbamcr.2008.11.010
CAS PubMed Article Google Scholar
Gonzales CB, Kirma NB, De La Chapa JJ, Chen R, Henry MA, Luo S, Hargreaves KM (2014) Vanilloids induce oral cancer apoptosis independent of TRPV1. Oral Oncol 50:437–447. doi:10.1016/j.oraloncology.2013.12.023
CAS PubMed PubMed Central Article Google Scholar
Guo H, Carlson JA, Slominski A (2012) Role of TRPM in melanocytes and melanoma. Exp Dermatol 21:650–654. doi:10.1111/j.1600-0625.2012.01565.x
CAS PubMed PubMed Central Article Google Scholar
Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695. doi:10.1016/j.cell.2006.11.001
CAS PubMed Article Google Scholar
Hayashi T, Kondo T, Ishimatsu M, Takeya M, Igata S, Nakamura K, Matsuoka K (2011) Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats. Auton Neurosci 164:27–33. doi:10.1016/j.autneu.2011.05.006
CAS PubMed Article Google Scholar
Hecquet CM, Zhang M, Mittal M, Vogel SM, Di A, Gao X, Bonini MG, Malik AB (2014) Cooperative interaction of trp melastatin channel transient receptor potential (TRPM2) with its splice variant TRPM2 short variant is essential for endothelial cell apoptosis. Circ Res 114:469–479. doi:10.1161/CIRCRESAHA.114.302414
CAS PubMed Article Google Scholar
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96. doi:10.3322/CA.2007.0010
PubMed Article Google Scholar
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249. doi:10.3322/caac.20006
PubMed Article Google Scholar
Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, Nuovo GJ, Lovat F, LeBlanc K, Palatini J, Randall RL, Volinia S, Stein GS, Croce CM, Lian JB, Aqeilan RI (2012) miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res 72:1865–1877. doi:10.1158/0008-5472.CAN-11-2663
CAS PubMed PubMed Central Article Google Scholar
Joshi G, Singh PK, Negi A, Rana A, Singh S, Kumar R (2015) Growth factors mediated cell signalling in prostate cancer progression: implications in discovery of anti-prostate cancer agents. Chem Biol Interact 240:120–133. doi:10.1016/j.cbi.2015.08.009
CAS PubMed Article Google Scholar
Journigan VB, Zaveri NT (2013) TRPM8 ion channel ligands for new therapeutic applications and as probes to study menthol pharmacology. Life Sci 92:425–437. doi:10.1016/j.lfs.2012.10.032
CAS PubMed Article Google Scholar
Jun JH, Kang HJ, Jin MH, Lee HY, Im YJ, Jung HJ, Han SW (2012) Function of the cold receptor (TRPM8) associated with voiding dysfunction in bladder outlet obstruction in rats. Int Neurourol J 16:69–76. doi:10.5213/inj.2012.16.2.69
PubMed PubMed Central Article Google Scholar
Keh SM, Facer P, Yehia A, Sandhu G, Saleh HA, Anand P (2011) The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis. Rhinology 49:453–457. doi:10.4193/Rhino11.089
CAS PubMed Google Scholar
Kijpornyongpan T, Sereemaspun A, Chanchao C (2014) Dose-dependent cytotoxic effects of menthol on human malignant melanoma A-375 cells: correlation with TRPM8 transcript expression. Asian Pac J Cancer Prev 15:1551–1556
PubMed Article Google Scholar
Klasen K, Hollatz D, Zielke S, Gisselmann G, Hatt H, Wetzel CH (2012) The TRPM8 ion channel comprises direct Gq protein-activating capacity. Pflug Arch 463:779–797. doi:10.1007/s00424-012-1098-7
CAS Article Google Scholar
Knowlton WM, McKemy DD (2011) TRPM8: from cold to cancer, peppermint to pain. Curr Pharm Biotechnol 12:68–77
CAS PubMed Article Google Scholar
Kong YH, Syed Zanaruddin SN, Lau SH, Ramanathan A, Kallarakkal TG, Vincent-Chong VK, Wan Mustafa WM, Abraham MT, Abdul Rahman ZA, Zain RB, Cheong SC (2015) Co-expression of TWIST1 and ZEB2 in oral squamous cell carcinoma is associated with poor survival. PLoS One 10:e0134045. doi:10.1371/journal.pone.0134045
PubMed PubMed Central Article CAS Google Scholar
Kono T, Satomi M, Suno M, Kimura N, Yamazaki H, Furukawa H, Matsubara K (2012) Oxaliplatin-induced neurotoxicity involves TRPM8 in the mechanism of acute hypersensitivity to cold sensation. Brain Behav 2:68–73. doi:10.1002/brb3.34
PubMed PubMed Central Article Google Scholar
Kulkarni P (2009) TRPM8 and prostate cancer: to overexpress or repress, that is the question-comment on “Effects of TRPM8 on proliferation and motility of prostate cancer PC-3 cells” by Yang ZH et al. in Asian Journal of Andrology. Asian J Androl 11:150–151. doi:10.1038/aja.2009.13
PubMed PubMed Central Article Google Scholar
Landsberg JW, Yuan JX (2004) Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 19:44–50
CAS PubMed Google Scholar
Lashinger ES, Steiginga MS, Hieble JP, Leon LA, Gardner SD, Nagilla R, Davenport EA, Hoffman BE, Laping NJ, Su X (2008) AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 295:F803–F810. doi:10.1152/ajprenal.90269.2008
CAS PubMed Article Google Scholar
Lehto SG, Weyer AD, Zhang M, Youngblood BD, Wang J, Wang W, Kerstein PC, Davis C, Wild KD, Stucky CL, Gavva NR (2015) AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia. Naunyn Schmiedebergs Arch Pharmacol 388:465–476. doi:10.1007/s00210-015-1090-9
CAS PubMed PubMed Central Article Google Scholar
Li Q, Wang X, Yang Z, Wang B, Li S (2009) Menthol induces cell death via the TRPM8 channel in the human bladder cancer cell line T24. Oncology 77:335–341. doi:10.1159/000264627
CAS PubMed Article Google Scholar
Liapis V, Labrinidis A, Zinonos I, Hay S, Ponomarev V, Panagopoulos V, DeNichilo M, Ingman W, Atkins GJ, Findlay DM, Zannettino AC, Evdokiou A (2015) Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma. Cancer Lett 357:160–169. doi:10.1016/j.canlet.2014.11.020
CAS PubMed Article Google Scholar
Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE (2013) TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. Pain 154:2169–2177. doi:10.1016/j.pain.2013.06.043
CAS PubMed PubMed Central Article Google Scholar
Liu B, Qin F (2005) Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:1674–1681. doi:10.1523/JNEUROSCI.3632-04.2005
CAS PubMed Article Google Scholar
Liu J, Chen Y, Shuai S, Ding D, Li R, Luo R (2014) TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via activating AKT/GSK-3beta pathway. Tumour Biol 35:8969–8977. doi:10.1007/s13277-014-2077-8
CAS PubMed Article Google Scholar
Lu S, Slominski A, Yang SE, Sheehan C, Ross J, Carlson JA (2010) The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi. J Cutan Pathol 37(Suppl. 1):26–40. doi:10.1111/j.1600-0560.2010.01504.x
PubMed PubMed Central Article Google Scholar
Madrid R, Donovan-Rodriguez T, Meseguer V, Acosta MC, Belmonte C, Viana F (2006) Contribution of TRPM8 channels to cold transduction in primary sensory neurons and peripheral nerve terminals. J Neurosci 26:12512–12525. doi:10.1523/JNEUROSCI.3752-06.2006
CAS PubMed Article Google Scholar
Malkia A, Pertusa M, Fernandez-Ballester G, Ferrer-Montiel A, Viana F (2009) Differential role of the menthol-binding residue Y745 in the antagonism of thermally gated TRPM8 channels. Mol Pain 5:62. doi:10.1186/1744-8069-5-62
PubMed PubMed Central Article CAS Google Scholar
Masamoto Y, Kawabata F, Fushiki T (2009) Intragastric administration of TRPV1, TRPV3, TRPM8, and TRPA1 agonists modulates autonomic thermoregulation in different manners in mice. Biosci Biotechnol Biochem 73:1021–1027. doi:10.1271/bbb.80796
CAS PubMed Article Google Scholar
Matta JA, Ahern GP (2007) Voltage is a partial activator of rat thermosensitive TRP channels. J Physiol 585:469–482. doi:10.1113/jphysiol.2007.144287
CAS PubMed PubMed Central Article Google Scholar
McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58. doi:10.1038/nature719
CAS PubMed Article Google Scholar
Mergler S, Strowski MZ, Kaiser S, Plath T, Giesecke Y, Neumann M, Hosokawa H, Kobayashi S, Langrehr J, Neuhaus P, Plockinger U, Wiedenmann B, Grotzinger C (2007) Transient receptor potential channel TRPM8 agonists stimulate calcium influx and neurotensin secretion in neuroendocrine tumor cells. Neuroendocrinology 85:81–92. doi:10.1159/000101693
CAS PubMed Article Google Scholar
Merritt JE, Armstrong WP, Benham CD, Hallam TJ, Jacob R, Jaxa-Chamiec A, Leigh BK, McCarthy SA, Moores KE, Rink TJ (1990) SK&F 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem J 271:515–522
CAS PubMed PubMed Central Article Google Scholar
Meseguer V, Karashima Y, Talavera K, D'Hoedt D, Donovan-Rodriguez T, Viana F, Nilius B, Voets T (2008) Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole. J Neurosci 28:576–586. doi:10.1523/JNEUROSCI.4772-07.2008
CAS PubMed Article Google Scholar
Messmer MN, Netherby CS, Banik D, Abrams SI (2015) Tumor-induced myeloid dysfunction and its implications for cancer immunotherapy. Cancer Immunol Immunother 64:1–13. doi:10.1007/s00262-014-1639-3
CAS PubMed Article Google Scholar
Mistretta F, Buffi NM, Lughezzani G, Lista G, Larcher A, Fossati N, Abrate A, Dell’Oglio P, Montorsi F, Guazzoni G, Lazzeri M (2014) Bladder cancer and urothelial impairment: the role of TRPV1 as potential drug target. Biomed Res Int 2014:987149. doi:10.1155/2014/987149
PubMed PubMed Central Article Google Scholar
Montell C, Birnbaumer L, Flockerzi V (2002) The TRP channels, a remarkably functional family. Cell 108:595–598
CAS PubMed Article Google Scholar
Mukkamala A, Allam CL, Ellison JS, Hafez KS, Miller DC, Montgomery JS, Weizer AZ, Wolf JS Jr (2014) Tumor enucleation vs sharp excision in minimally invasive partial nephrectomy: technical benefit without impact on functional or oncologic outcomes. Urology 83:1294–1299. doi:10.1016/j.urology.2014.02.007
PubMed Article Google Scholar
Nakazawa Y, Arai H, Fujita N (2011) The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis. Cancer Res 71:1146–1155. doi:10.1158/0008-5472.CAN-10-2695
CAS PubMed Article Google Scholar
Ohmi M, Shishido Y, Inoue T, Ando K, Fujiuchi A, Yamada A, Watanabe S, Kawamura K (2014) Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist. Bioorg Med Chem Lett 24:5364–5368. doi:10.1016/j.bmcl.2014.10.074
CAS PubMed Article Google Scholar
Okamoto Y, Ohkubo T, Ikebe T, Yamazaki J (2012) Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines. Int J Oncol 40:1431–1440. doi:10.3892/ijo.2012.1340
CAS PubMed Google Scholar
Patel R, Goncalves L, Newman R, Jiang FL, Goldby A, Reeve J, Hendrick A, Teall M, Hannah D, Almond S, Brice N, Dickenson AH (2014) Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats. J Pharmacol Exp Ther 349:47–55. doi:10.1124/jpet.113.211243
PubMed Article CAS Google Scholar
Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715
CAS PubMed Article Google Scholar
Raddatz N, Castillo JP, Gonzalez C, Alvarez O, Latorre R (2014) Temperature and voltage coupling to channel opening in transient receptor potential melastatin 8 (TRPM8). J Biol Chem 289:35438–35454. doi:10.1074/jbc.M114.612713
CAS PubMed PubMed Central Article Google Scholar
Rohacs T, Lopes CM, Michailidis I, Logothetis DE (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci 8:626–634. doi:10.1038/nn1451
CAS PubMed Article Google Scholar
Saadoun H, Lamy PJ, Thezenas S, Pouderoux S, Bibeau F, Montels F, Romieu G, Colombo PE, Gutowski M, Jacot W (2014) Prognostic impact of the inclusion of uPA/PAI-1 tumor levels in the current adjuvant treatment decision-making for early breast cancer. Future Oncol 10:195–209. doi:10.2217/fon.13.177
CAS PubMed Article Google Scholar
Sanchez MG, Sanchez AM, Collado B, Malagarie-Cazenave S, Olea N, Carmena MJ, Prieto JC, Diaz-Laviada II (2005) Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol 515:20–27. doi:10.1016/j.ejphar.2005.04.010
CAS PubMed Article Google Scholar
Shoeneman JK, Ehrhart EJ 3rd, Eickhoff JC, Charles JB, Powers BE, Thamm DH (2012) Expression and function of survivin in canine osteosarcoma. Cancer Res 72:249–259. doi:10.1158/0008-5472.CAN-11-2315
CAS PubMed Article Google Scholar
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30. doi:10.3322/caac.21166
PubMed Article Google Scholar
Slominski A (2008) Cooling skin cancer: menthol inhibits melanoma growth. Focus on “TRPM8 activation suppresses cellular viability in human melanoma”. Am J Physiol Cell Physiol 295:C293–C295. doi:10.1152/ajpcell.00312.2008
CAS PubMed PubMed Central Article Google Scholar
Sotiropoulou N, Bravou V, Kounelis S, Damaskou V, Papaspirou E, Papadaki H (2010) Tumour expression of lymphangiogenic growth factors but not lymphatic vessel density is implicated in human cervical cancer progression. Pathology 42:629–636. doi:10.3109/00313025.2010.522174
PubMed Article Google Scholar
Su L, Wang C, Yu YH, Ren YY, Xie KL, Wang GL (2011) Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain. BMC Neurosci 12:120. doi:10.1186/1471-2202-12-120
CAS PubMed PubMed Central Article Google Scholar
Sun W, Zhang X, Ding X, Li H, Geng M, Xie Z, Wu H, Huang M (2015) Lactate dehydrogenase B is associated with the response to neoadjuvant chemotherapy in oral squamous cell carcinoma. PLoS One 10:e0125976. doi:10.1371/journal.pone.0125976
PubMed PubMed Central Article CAS Google Scholar
Takaishi M, Fujita F, Uchida K, Yamamoto S, Sawada Shimizu M, Hatai Uotsu C, Shimizu M, Tominaga M (2012) 1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1. Mol Pain 8:86. doi:10.1186/1744-8069-8-86
CAS PubMed PubMed Central Article Google Scholar
Than JY, Li L, Hasan R, Zhang X (2013) Excitation and modulation of TRPA1, TRPV1, and TRPM8 channel-expressing sensory neurons by the pruritogen chloroquine. J Biol Chem 288:12818–12827. doi:10.1074/jbc.M113.450072
PubMed PubMed Central Article CAS Google Scholar
Tsavaler L, Shapero MH, Morkowski S, Laus R (2001) Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61:3760–3769
CAS PubMed Google Scholar
Valero M, Morenilla-Palao C, Belmonte C, Viana F (2011) Pharmacological and functional properties of TRPM8 channels in prostate tumor cells. Pflug Arch 461:99–114. doi:10.1007/s00424-010-0895-0
CAS Article Google Scholar
Valero ML, Mello de Queiroz F, Stuhmer W, Viana F, Pardo LA (2012) TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. PLoS One 7:e51825. doi:10.1371/journal.pone.0051825
CAS PubMed PubMed Central Article Google Scholar
Vanden Abeele F, Zholos A, Bidaux G, Shuba Y, Thebault S, Beck B, Flourakis M, Panchin Y, Skryma R, Prevarskaya N (2006) Ca²⁺-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids. J Biol Chem 281:40174–40182. doi:10.1074/jbc.M605779200
CAS PubMed Article Google Scholar
Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430:748–754. doi:10.1038/nature02732
CAS PubMed Article Google Scholar
von Thaler AK, Kamenisch Y, Berneburg M (2010) The role of ultraviolet radiation in melanomagenesis. Exp Dermatol 19:81–88. doi:10.1111/j.1600-0625.2009.01025.x
Article CAS Google Scholar
Wang G, Lemos JR, Iadecola C (2004) Herbal alkaloid tetrandrine: from an ion channel blocker to inhibitor of tumor proliferation. Trends Pharmacol Sci 25:120–123
CAS PubMed Article Google Scholar
Wang Y, Wang X, Yang Z, Zhu G, Chen D, Meng Z (2012) Menthol inhibits the proliferation and motility of prostate cancer DU145 cells. Pathol Oncol Res 18:903–910. doi:10.1007/s12253-012-9520-1
CAS PubMed Article Google Scholar
Wang Y, Yang Z, Meng Z, Cao H, Zhu G, Liu T, Wang X (2013) Knockdown of TRPM8 suppresses cancer malignancy and enhances epirubicin-induced apoptosis in human osteosarcoma cells. Int J Biol Sci 10:90–102. doi:10.7150/ijbs.7738
CAS PubMed PubMed Central Article Google Scholar
Weil A, Moore SE, Waite NJ, Randall A, Gunthorpe MJ (2005) Conservation of functional and pharmacological properties in the distantly related temperature sensors TRVP1 and TRPM8. Mol Pharmacol 68:518–527. doi:10.1124/mol.105.012146
CAS PubMed Google Scholar
Winchester WJ, Gore K, Glatt S, Petit W, Gardiner JC, Conlon K, Postlethwaite M, Saintot PP, Roberts S, Gosset JR, Matsuura T, Andrews MD, Glossop PA, Palmer MJ, Clear N, Collins S, Beaumont K, Reynolds DS (2014) Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. J Pharmacol Exp Ther 351:259–269. doi:10.1124/jpet.114.216010
PubMed Article CAS Google Scholar
Wondergem R, Ecay TW, Mahieu F, Owsianik G, Nilius B (2008) HGF/SF and menthol increase human glioblastoma cell calcium and migration. Biochem Biophys Res Commun 372:210–215. doi:10.1016/j.bbrc.2008.05.032
CAS PubMed Article Google Scholar
Wu XY, Ma W, Gurung K, Guo CH (2013) Mechanisms of tumor resistance to small-molecule vascular disrupting agents: treatment and rationale of combination therapy. J Formos Med Assoc 112:115–124. doi:10.1016/j.jfma.2012.09.017
CAS PubMed Article Google Scholar
Wu TT, Peters AA, Tan PT, Roberts-Thomson SJ, Monteith GR (2014) Consequences of activating the calcium-permeable ion channel TRPV1 in breast cancer cells with regulated TRPV1 expression. Cell Calcium 56:59–67. doi:10.1016/j.ceca.2014.04.006
CAS PubMed Article Google Scholar
Yamamura H, Ugawa S, Ueda T, Morita A, Shimada S (2008) TRPM8 activation suppresses cellular viability in human melanoma. Am J Physiol Cell Physiol 295:C296–C301. doi:10.1152/ajpcell.00499.2007
CAS PubMed Article Google Scholar
Yee NS, Brown RD, Lee MS, Zhou W, Jensen C, Gerke H, Yee RK (2012a) TRPM8 ion channel is aberrantly expressed and required for preventing replicative senescence in pancreatic adenocarcinoma: potential role of TRPM8 as a biomarker and target. Cancer Biol Ther 13:592–599. doi:10.4161/cbt.20079
CAS PubMed PubMed Central Article Google Scholar
Yee NS, Chan AS, Yee JD, Yee RK (2012b) TRPM7 and TRPM8 ion channels in pancreatic adenocarcinoma: potential roles as cancer biomarkers and targets. Scientifica 2012:415158. doi:10.6064/2012/415158
PubMed PubMed Central Article CAS Google Scholar
Yee NS, Li Q, Kazi AA, Yang Z, Berg A, Yee RK (2014) Aberrantly over-expressed TRPM8 channels in pancreatic adenocarcinoma: correlation with tumor size/stage and requirement for cancer cells invasion. Cells 3:500–516. doi:10.3390/cells3020500
PubMed PubMed Central Article CAS Google Scholar
Yu S, Xu Z, Zou C, Wu D, Wang Y, Yao X, Ng CF, Chan FL (2014) Ion channel TRPM8 promotes hypoxic growth of prostate cancer cells via an O2-independent and RACK1-mediated mechanism of HIF-1alpha stabilization. J Pathol 234:514–525. doi:10.1002/path.4413
CAS PubMed Article Google Scholar
Yudin Y, Rohacs T (2012) Regulation of TRPM8 channel activity. Mol Cell Endocrinol 353:68–74. doi:10.1016/j.mce.2011.10.023
CAS PubMed Article Google Scholar
Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T (2009) Inorganic polyphosphate modulates TRPM8 channels. PLoS One 4:e5404. doi:10.1371/journal.pone.0005404
PubMed PubMed Central Article CAS Google Scholar
Zakharian E, Cao C, Rohacs T (2010) Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers. J Neurosci 30:12526–12534. doi:10.1523/JNEUROSCI.3189-10.2010
CAS PubMed PubMed Central Article Google Scholar
Zhang L, Barritt GJ (2004) Evidence that TRPM8 is an androgen-dependent Ca²⁺ channel required for the survival of prostate cancer cells. Cancer Res 64:8365–8373. doi:10.1158/0008-5472.CAN-04-2146
CAS PubMed Article Google Scholar
Zhang X, Mak S, Li L, Parra A, Denlinger B, Belmonte C, McNaughton PA (2012) Direct inhibition of the cold-activated TRPM8 ion channel by Galphaq. Nat Cell Biol 14:851–858. doi:10.1038/ncb2529
CAS PubMed PubMed Central Article Google Scholar
Zhang L, Yuan H, Inscoe C, Chtcheprov P, Hadsell M, Lee Y, Lu J, Chang S, Zhou O (2014) Nanotube X-ray for cancer therapy: a compact microbeam radiation therapy system for brain tumor treatment. Expert Rev Anticancer Ther 14:1411–1418. doi:10.1586/14737140.2014.978293
CAS PubMed PubMed Central Article Google Scholar
Zheng T, Yin D, Lu Z, Wang J, Li Y, Chen X, Liang Y, Song X, Qi S, Sun B, Xie C, Meng X, Pan S, Liu J, Jiang H, Liu L (2014) Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in hepatocellular carcinoma. Mol Cancer 13:133. doi:10.1186/1476-4598-13-133
PubMed PubMed Central Article CAS Google Scholar
Zhu G, Wang X, Yang Z, Cao H, Meng Z, Wang Y, Chen D (2011) Effects of TRPM8 on the proliferation and angiogenesis of prostate cancer PC-3 cells in vivo. Oncol Lett 2:1213–1217. doi:10.3892/ol.2011.410
CAS PubMed PubMed Central Google Scholar

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Acknowledgments

The authors thank the financial support from the National Natural Science Foundation of China (Nos. 81173174, 81202655, and 81403260); 2013 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education; A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Jiangsu College graduate research and innovation projects (Nos. CXLX12_0587 and KYZZ_0270).

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Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, Jiangsu, People’s Republic of China
Zhaoguo Liu, Hongyan Wu, Zhonghong Wei, Xu Wang, Peiliang Shen, Siliang Wang, Aiyun Wang, Wenxing Chen & Yin Lu
Department of Pharmacy, Yancheng Health Vocational and Technical College, Yancheng, 224005, Jiangsu Province, China
Hongyan Wu
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China
Yin Lu

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Zhaoguo Liu
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Hongyan Wu
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Zhonghong Wei
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Xu Wang
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Peiliang Shen
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Siliang Wang
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Aiyun Wang
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Wenxing Chen
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Yin Lu
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Zhaoguo Liu and Hongyan Wu have contributed equally to this work.

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Liu, Z., Wu, H., Wei, Z. et al. TRPM8: a potential target for cancer treatment. J Cancer Res Clin Oncol 142, 1871–1881 (2016). https://doi.org/10.1007/s00432-015-2112-1

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Received: 22 December 2015
Accepted: 28 December 2015
Published: 23 January 2016
Issue Date: September 2016
DOI: https://doi.org/10.1007/s00432-015-2112-1

Keywords

TRPM8
Thermoregulation
Pain transduction
Tumor
Anti-cancer therapy