Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

doi:10.3390/biom11050765

Review

. 2021 May 20;11(5):765.

doi: 10.3390/biom11050765.

Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

Federica Maggi^{1

2}, Maria Beatrice Morelli², Massimo Nabissi², Oliviero Marinelli², Laura Zeppa², Cristina Aguzzi², Giorgio Santoni², Consuelo Amantini³

Affiliations

¹ Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy.
² Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy.
³ Immunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.

PMID: 34065398
PMCID: PMC8160608
DOI: 10.3390/biom11050765

Review

Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

Federica Maggi et al. Biomolecules. 2021.

. 2021 May 20;11(5):765.

doi: 10.3390/biom11050765.

Authors

Federica Maggi^{1

2}, Maria Beatrice Morelli², Massimo Nabissi², Oliviero Marinelli², Laura Zeppa², Cristina Aguzzi², Giorgio Santoni², Consuelo Amantini³

Affiliations

¹ Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy.
² Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy.
³ Immunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.

PMID: 34065398
PMCID: PMC8160608
DOI: 10.3390/biom11050765

Abstract

Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the perspective of personalised therapies.

Keywords: TRP; leukaemia; lymphoma.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

**Figure 1**
Structure and localisation of TRP channels: (A) structural domains and motifs in the N- and C- terminus of TRP channel subfamilies [7]; (B) intracellular localisation of TRP channel subfamilies and SOCE machinery. Abbreviations: TRPA, transient receptor potential ankyrin; TRPC, transient receptor potential canonical; TRPM, transient receptor potential melastatin; TRPML, transient receptor potential mucolipidin; TRPP, transient receptor potential polycystic; TRPV, transient receptor potential vanilloid; ER, endoplasmatic reticulum; EV, vesicle of exocytosis; EE, early endosome; RE, recycling endosome; LE, late endosome; PM, plasma membrane; STIM1, stromal interaction molecule 1; Orai1, calcium release-activated calcium channel protein 1.

**Figure 2**
TRPM2 depletion has been correlated with the impairment of several pathways essential for the survival of leukemic cancer cells, suggesting TRPM2 as a strategic therapeutic _target [48,49,70]. Abbreviations: HSC, hematopoietic stem cells; GMP, granulocyte-macrophage progenitors; AML, acute myeloid leukaemia; TRPM2, transient receptor potential melastatin 2; HIF 1/2α, hypoxia-inducible factor 1/2α; FOXO3a, forkhead box O3a; Nrf2, nuclear factor erythroid 2–related factor 2; ULK1, Unc-51 like autophagy activating kinase 1; Atg7, autophagy-related 7; Atg5, autophagy-related 5; ATP, adenosine triphosphate; OCR, oxygen consumption rate; Tom20, translocase of outer membrane 20; KO, knockout; (↑) increment; (↓) reduction.

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References

1. Nilius B. TRP channels in disease. Biochim. Biophys. Acta Mol. Basis Dis. 2007;1772:805–812. doi: 10.1016/j.bbadis.2007.02.002. - DOI - PubMed
1. Ramsey I.S., Delling M., Clapham D.E. An introduction to TRP channels. Annu. Rev. Physiol. 2006;68:619–647. doi: 10.1146/annurev.physiol.68.040204.100431. - DOI - PubMed
1. Montell C., Rubin G.M. Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction. Neuron. 1989;2:1313–1323. doi: 10.1016/0896-6273(89)90069-X. - DOI - PubMed
1. Zheng J. Comprehensive Physiology. Volume 3. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2013. Molecular Mechanism of TRP Channels; pp. 221–242. - PMC - PubMed
1. Duan J., Li Z., Li J., Hulse R.E., Santa-Cruz A., Valinsky W.C., Abiria S.A., Krapivinsky G., Zhang J., Clapham D.E. Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc. Natl. Acad. Sci. USA. 2018;115:E8201–E8210. doi: 10.1073/pnas.1810719115. - DOI - PMC - PubMed

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[1] Nilius B. TRP channels in disease. Biochim. Biophys. Acta Mol. Basis Dis. 2007;1772:805–812. doi: 10.1016/j.bbadis.2007.02.002. - DOI - PubMed

[2] Nilius B. TRP channels in disease. Biochim. Biophys. Acta Mol. Basis Dis. 2007;1772:805–812. doi: 10.1016/j.bbadis.2007.02.002. - DOI - PubMed

[3] Ramsey I.S., Delling M., Clapham D.E. An introduction to TRP channels. Annu. Rev. Physiol. 2006;68:619–647. doi: 10.1146/annurev.physiol.68.040204.100431. - DOI - PubMed

[4] Ramsey I.S., Delling M., Clapham D.E. An introduction to TRP channels. Annu. Rev. Physiol. 2006;68:619–647. doi: 10.1146/annurev.physiol.68.040204.100431. - DOI - PubMed

[5] Montell C., Rubin G.M. Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction. Neuron. 1989;2:1313–1323. doi: 10.1016/0896-6273(89)90069-X. - DOI - PubMed

[6] Montell C., Rubin G.M. Molecular characterization of the drosophila trp locus: A putative integral membrane protein required for phototransduction. Neuron. 1989;2:1313–1323. doi: 10.1016/0896-6273(89)90069-X. - DOI - PubMed

[7] Zheng J. Comprehensive Physiology. Volume 3. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2013. Molecular Mechanism of TRP Channels; pp. 221–242. - PMC - PubMed

[8] Zheng J. Comprehensive Physiology. Volume 3. John Wiley & Sons, Inc.; Hoboken, NJ, USA: 2013. Molecular Mechanism of TRP Channels; pp. 221–242. - PMC - PubMed

[9] Duan J., Li Z., Li J., Hulse R.E., Santa-Cruz A., Valinsky W.C., Abiria S.A., Krapivinsky G., Zhang J., Clapham D.E. Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc. Natl. Acad. Sci. USA. 2018;115:E8201–E8210. doi: 10.1073/pnas.1810719115. - DOI - PMC - PubMed

[10] Duan J., Li Z., Li J., Hulse R.E., Santa-Cruz A., Valinsky W.C., Abiria S.A., Krapivinsky G., Zhang J., Clapham D.E. Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc. Natl. Acad. Sci. USA. 2018;115:E8201–E8210. doi: 10.1073/pnas.1810719115. - DOI - PMC - PubMed

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Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

Affiliations

Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

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Conflict of interest statement

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