关键词： 4α-PDD, 4α-phorbol-12,13-didecanoate ABCB, ATP-binding cassette B1 AKT, protein kinase B ALA, alpha lipoic acid AMPK, AMP-activated protein kinase APB, aminoethoxydiphenyl borate ATP, adenosine triphosphate CBD, cannabidiol CRAC, Ca2+ release-activated Ca2+ channel CaR, calcium-sensing receptor CaSR, calcium sensing receptor Cancer progression DAG, diacylglycerol DBTRG, Denver Brain Tumor Research Group ECFC, endothelial colony-forming cells ECM, enhanced extracellular matrix EGF, epidermal growth factor EMT, epithelial–mesenchymal transition ER, endoplasmic reticulum ERK, extracellular signal-regulated kinase ETS, erythroblastosis virus E26 oncogene homolog FAK, focal adhesion kinase GADD, growth arrest and DNA damage-inducible gene GC, gastric cancer GPCR, G-protein coupled receptor GSC, glioma stem-like cells GSK, glycogen synthase kinase HCC, hepatocellular carcinoma HIF, hypoxia-induced factor HSC, hematopoietic stem cells IP3R, inositol triphosphate receptor Intracellular mechanism KO, knockout LOX, lipoxygenase LPS, lipopolysaccharide LRP, lipoprotein receptor-related protein MAPK, mitogen-activated protein kinase MLKL, mixed lineage kinase domain-like protein MMP, matrix metalloproteinases NEDD4, neural precursor cell expressed, developmentally down-regulated 4 NFAT, nuclear factor of activated T-cells NLRP3, NLR family pyrin domain containing 3 NO, nitro oxide NSCLC, non-small cell lung cancer Nrf2, nuclear factor erythroid 2-related factor 2 P-gp, P-glycoprotein PCa, prostate cancer PDAC, pancreatic ductal adenocarcinoma PHD, prolyl hydroxylases PI3K, phosphoinositide 3-kinase PKC, protein kinase C PKD, polycystic kidney disease PLC, phospholipase C Programmed cancer cell death RNS/ROS, reactive nitrogen species/reactive oxygen species RTX, resiniferatoxin SMAD, Caenorhabditis elegans protein (Sma) and mothers against decapentaplegic (Mad) SOCE, store operated calcium entry SOR, soricimed STIM1, stromal interaction molecules 1 TEC, tumor endothelial cells TGF, transforming growth factor-β TNF-α, tumor necrosis factor-α TRP channels TRPA/C/M/ML/N/P/V, transient receptor potential ankyrin/canonical/melastatin/mucolipon/NOMPC/polycystin/vanilloid Targeted tumor therapy Tumor microenvironment Tumor-associated immunocytes UPR, unfolded protein response VEGF, vascular endothelial growth factor VIP, vasoactive intestinal peptide VPAC, vasoactive intestinal peptide receptor subtype mTOR, mammalian target of rapamycin pFRG/RTN, parafacial respiratory group/retrotrapezoid nucleus 4α-PDD, 4α-phorbol-12,13-didecanoate ABCB, ATP-binding cassette B1 AKT, protein kinase B ALA, alpha lipoic acid AMPK, AMP-activated protein kinase APB, aminoethoxydiphenyl borate ATP, adenosine triphosphate CBD, cannabidiol CRAC, Ca2+ release-activated Ca2+ channel CaR, calcium-sensing receptor CaSR, calcium sensing receptor Cancer progression DAG, diacylglycerol DBTRG, Denver Brain Tumor Research Group ECFC, endothelial colony-forming cells ECM, enhanced extracellular matrix EGF, epidermal growth factor EMT, epithelial–mesenchymal transition ER, endoplasmic reticulum ERK, extracellular signal-regulated kinase ETS, erythroblastosis virus E26 oncogene homolog FAK, focal adhesion kinase GADD, growth arrest and DNA damage-inducible gene GC, gastric cancer GPCR, G-protein coupled receptor GSC, glioma stem-like cells GSK, glycogen synthase kinase HCC, hepatocellular carcinoma HIF, hypoxia-induced factor HSC, hematopoietic stem cells IP3R, inositol triphosphate receptor Intracellular mechanism KO, knockout LOX, lipoxygenase LPS, lipopolysaccharide LRP, lipoprotein receptor-related protein MAPK, mitogen-activated protein kinase MLKL, mixed lineage kinase domain-like protein MMP, matrix metalloproteinases NEDD4, neural precursor cell expressed, developmentally down-regulated 4 NFAT, nuclear factor of activated T-cells NLRP3, NLR family pyrin domain containing 3 NO, nitro oxide NSCLC, non-small cell lung cancer Nrf2, nuclear factor erythroid 2-related factor 2 P-gp, P-glycoprotein PCa, prostate cancer PDAC, pancreatic ductal adenocarcinoma PHD, prolyl hydroxylases PI3K, phosphoinositide 3-kinase PKC, protein kinase C PKD, polycystic kidney disease PLC, phospholipase C Programmed cancer cell death RNS/ROS, reactive nitrogen species/reactive oxygen species RTX, resiniferatoxin SMAD, Caenorhabditis elegans protein (Sma) and mothers against decapentaplegic (Mad) SOCE, store operated calcium entry SOR, soricimed STIM1, stromal interaction molecules 1 TEC, tumor endothelial cells TGF, transforming growth factor-β TNF-α, tumor necrosis factor-α TRP channels TRPA/C/M/ML/N/P/V, transient receptor potential ankyrin/canonical/melastatin/mucolipon/NOMPC/polycystin/vanilloid Targeted tumor therapy Tumor microenvironment Tumor-associated immunocytes UPR, unfolded protein response VEGF, vascular endothelial growth factor VIP, vasoactive intestinal peptide VPAC, vasoactive intestinal peptide receptor subtype mTOR, mammalian target of rapamycin pFRG/RTN, parafacial respiratory group/retrotrapezoid nucleus

来  源：   DOI：10.1016/j.apsb.2021.11.001   PDF(Pubmed)

Abstract：
Transient receptor potential (TRP) channels are one primary type of calcium (Ca2+) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive. Therefore, in this review, we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, and the alterations of relevant tumor micro-environment. Moreover, we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors\' efficacy. The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented. Furthermore, it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.
摘要：
瞬时受体电位(TRP)通道是钙(Ca2+)通透性通道的主要类型,这些相关的跨膜和细胞内TRP通道以前被认为主要与心血管和神经元系统的调节有关。如今,然而,越来越多的证据表明，这些TRP通道也负责肿瘤发生和发展，诱导肿瘤侵袭和转移。然而,TRP通道在恶性肿瘤中的总体潜在机制和可能的信号转导途径可能仍然难以捉摸.因此,在这次审查中,我们专注于TRP通道与肿瘤的显着特征之间的联系，例如多药耐药（MDR），转移,凋亡，扩散,逃避免疫监视，以及相关肿瘤微环境的改变。此外，我们还讨论了相关TRP通道在各种形式癌症中的表达和相关抑制剂的疗效。还介绍了各种作用机制的抗癌药物的化学敏感性和潜在的临床应用。此外，对于这种类型的钙通道的干预，提供可能的新的治疗方法来对抗恶性肿瘤将是有启发性的。
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