Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

Mistretta, Francesco A.; Buffi, Nicolò Maria; Lughezzani, Giovanni; Lista, Giuliana; Larcher, Alessandro; Fossati, Nicola; Abrate, Alberto; Dell’Oglio, Paolo; Montorsi, Francesco; Guazzoni, G.; Lazzeri, Massimo

doi:10.1155/2014/987149

Cited by 30 publications

(20 citation statements)

References 99 publications

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“…However, it is unknown whether these changes in TRP expression are central to the success of the cancer or are a secondary step to other cellular modifications (Mistretta et al, 2014). The nature of cancer cells, tumor progression, and metastatic spreading might be implicated in mutations and in the altered expression of numerous key signaling proteins such as TRP channels (Prevarskaya et al, 2007).…”

Section: Calcium Channel-associated Transientmentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calciumpermeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca 21 activity plays an important role in the regulation of cell proliferation, and Ca 21 signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca 21 by modulating the driving force for Ca 21 entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca 21 -influx and an indirect activator of voltage-gated Ca 21 -channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca 21 , and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

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Section: Calcium Channel-associated Transientmentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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“…Beyond nociception, an increasing number of studies provide emerging evidence that TRPV1 is involved in diverse human physiologies and pathophysiologies including: inflammatory diseases (10)(11)(12), obesity (13,14), diabetes (11), longevity (15), and cancer (16,17).…”

Section: Introductionmentioning

confidence: 99%

Evidence that the TRPV1 S1-S4 Membrane Domain Contributes to Thermosensing

Kim

Sisco

Hilton

et al. 2019

Preprint

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Sensing and responding to temperature is crucial in biology. The TRPV1 ion channel is a well-studied heat-sensing receptor that is also activated by vanilloid compounds including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive. The TRPV1 S1-S4 membrane domain couples chemical ligand binding to the pore domain during channel gating.However, the role of the S1-S4 domain in thermosensing is unclear. Evaluation of the isolated human TRPV1 S1-S4 domain by solution NMR, Far-UV CD, and intrinsic fluorescence shows that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity. Further NMR characterization of the temperature-dependent conformational changes suggests the contribution of the S1-S4 domain to thermosensing shares features with known coupling mechanisms between this domain with ligand and pH activation. Taken together, this study shows that the TRPV1 S1-S4 domain contributes to TRPV1 temperature-dependent activation.

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“…TRP channels play an important role in the development of several diseases, and one of the most investigated and described TRP channel is TRPV1 10. TRPV1 agonist, capsaicin, is capable of inducing apoptosis11,12 and inhibiting cancer cell growth by cell cycle arrest in many different types of cancer, for example, osteosarcoma, colon, and pancreatic cancer cells, while normal cells remained unharmed 13–17. A less-pungent capsaicin-like analog, RPF151, showed antitumor activity in a murine breast cancer model in vivo,18 demonstrating the possibility of managing the induction of pain.…”

Section: Introductionmentioning

confidence: 99%

Expression and functionality of TRPV1 in breast cancer cells

Weber¹,

Al-Refae²,

Wölk³

et al. 2016

BCTT

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Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer progression; however, no study has examined the expression profiles of human TRP channels in breast cancer on a large scale. This study focused on the expression and functionality of TRPV1, a nonselective cation channel that was found to be expressed in different carcinoma tissues. Next-generation sequencing analyses revealed the expression of TRPV1 in several native breast cancer tissues, which was subsequently validated via reverse transcriptase-polymerase chain reaction. Activation of TRPV1 by its ligand capsaicin was associated with the growth inhibition of some cancer cell types; however, the signaling components involved are complex. In this study, stimulation by the TRPV1 agonist, capsaicin, of SUM149PT cells, a model system for the most aggressive breast cancer subtype, triple-negative breast cancer, led to intracellular calcium signals that were diminished by the specific TRPV1 antagonist, capsazepin. Activation of TRPV1 by capsaicin caused significant inhibition of cancer cell growth and induced apoptosis and necrosis. In conclusion, the current study revealed the expression profiles of human TRP channels in 60 different breast cancer tissues and cell lines and furthermore validated the antitumor activity of TRPV1 against SUM149PT breast cancer cells, indicating that activation of TRPV1 could be used as a therapeutic target, even in the most aggressive breast cancer types.

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Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

Cited by 30 publications

References 99 publications

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Evidence that the TRPV1 S1-S4 Membrane Domain Contributes to Thermosensing

Expression and functionality of TRPV1 in breast cancer cells

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