The combination of TRPM8 and TRPA1 expression causes an invasive phenotype in lung cancer

Du, Gangjun; Li, Jiahuan; Liu, Weijie; Liu, Yinghui; Zhao, Bin; Li, Hongru; Hou, Xidong; Li, Hong; Qi, Xiaoxiao; Duan, Yongjian

doi:10.1007/s13277-013-1167-3

Cited by 53 publications

(39 citation statements)

References 34 publications

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“…The cation channels TRPA1 and RyR detect oxidative stress associated with tissue damage and mediate increases in cytosolic Ca 2+ in ISCs to amplify and activate EGFR-Ras/MAPK signaling (Figure 8). In vertebrates, a number of cation channels (Monteith et al, 2007), including TRPA1 and RyR (Abdul et al, 2008; Büch et al, 2013; Du et al, 2014), have been associated with tumor malignancy. Our findings, unraveling the relationship between redox-sensing, cytosolic Ca 2+ , and pro-mitosis Ras/MAPK activity in ISCs, could potentially help understand the roles of cation channels in stem cells and cancers, and inspire novel pharmacological interventions to improve stem cell activity for regeneration purposes and suppress tumorigenic growth of stem cells.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut

Luo

et al. 2017

eLife

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Precise regulation of stem cell activity is crucial for tissue homeostasis and necessary to prevent overproliferation. In the Drosophila adult gut, high levels of reactive oxygen species (ROS) has been detected with different types of tissue damage, and oxidative stress has been shown to be both necessary and sufficient to trigger intestinal stem cell (ISC) proliferation. However, the connection between oxidative stress and mitogenic signals remains obscure. In a screen for genes required for ISC proliferation in response to oxidative stress, we identified two regulators of cytosolic Ca2+ levels, transient receptor potential A1 (TRPA1) and ryanodine receptor (RyR). Characterization of TRPA1 and RyR demonstrates that Ca2+ signaling is required for oxidative stress-induced activation of the Ras/MAPK pathway, which in turns drives ISC proliferation. Our findings provide a link between redox regulation and Ca2+ signaling and reveal a novel mechanism by which ISCs detect stress signals.DOI: http://dx.doi.org/10.7554/eLife.22441.001

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Section: Discussionmentioning

confidence: 99%

Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut

Luo

et al. 2017

eLife

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“…Higher expression levels of TRPM8 mRNA in prostate cancer tissues than those in patient-matched noncancerous prostate tissue was found by semiquantitative RT-PCR, and TRPM8 expression was detectable only in androgen receptor (AR)-positive prostate cancer cells; furthermore, the study saw a higher expression of TRPM8 mRNA in the urine and blood of patients with metastatic prostate cancer than in those of healthy men [20]. TRPM8 knockdown using siRNA promoted cell proliferation and inhibited adhesion and invasiveness in Lewis lung cancer (LLC-2) cells [12]. Although TRPM8 expression and location were conformed previously in bladder cancer T24 cells [21], the expression levels of TRPM8 in UCB tissues and the relationship between TRPM8 expression and UCB clinicopathological characteristics remain to be poorly elucidated in the previous research.…”

Section: Discussionmentioning

confidence: 99%

“…In the subfamilies of TRP channels, TRP channel melastatin 8 (TRPM8) was identified and has been proposed to be the predominant thermoreceptor for cellular and behavioral responses to cold stimuli [7]. Although the aberrant expression of TRPM8 is detected in many tumors [8][9][10][11] and is represented as a key protein in central mechanisms of carcinogenesis, some disagreement of their roles in it was raised in different studies [12].…”

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confidence: 99%

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Xiao

Jiang

et al. 2014

Tumor Biol.

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Transient receptor protein (TRP) channels are frequently associated with tumors and are correlated to patient's outcome. We firstly investigated TRP channel melastatin 8 (TRPM8) expression in urothelial carcinoma of bladder (UCB) and its correlation with UCB clinicopathological features and additionally evaluated the association between TRPM8 expression and patients' survival rate to elucidate its role in bladder oncogenesis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to examine TRPM8 messenger RNA (mRNA) expression in 36 pairs of freshly frozen UCB tissues and matched noncancerous tissues. Immunohistochemistry (IHC) was performed in 156 archived paraffin-embedded UCB samples to explore the correlation between TRPM8 protein and clinicopathological features. The association between TRPM8 expression and patient's survival rate was evaluated using the Kaplan-Meier method and multivariate Cox regression analysis, respectively. The expression levels of TRPM8 mRNA in UCB tissues were significantly higher than those in matched noncancerous tissues (P=0.016). Expression of TRPM8 protein in UCB was significantly and positively associated with histological grade (P=0.039) and tumor stage (P=0.037). Significant correlation between high TRPM8 expression and poor cumulative survival of UCB patients was shown using the Kaplan-Meier survival curve (P=0.039). TRPM8 was represented as an independent prognostic biomarker for UCB patients by multivariate Cox regression analysis (P=0.047). The present study provide the convincing evidence for the first time that over-expression of TRPM8 may play a role in the pathogenesis and progression of UCB, and TRPM8 may serve as an independent prognostic biomarker for UCB patients.

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“…), and contribute to a more invasive phenotype in vitro (Du et al. ). TRPA1 has also been strongly implicated as a mediator of chemotherapy‐induced peripheral neuropathy (CIPN, Nassini et al.…”

Section: Discussionmentioning

confidence: 99%

Nordihydroguaiaretic acid activates hTRPA1 and modulates behavioral responses to noxious cold in mice

Redmond

Camo

Mitchell

et al. 2014

Pharmacology Res & Perspec

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Nordihydroguaiaretic acid (NDGA) is a major biologically active component of the creosote bush, Larrea tridentate, widely used in unregulated therapies. NDGA is a lipoxygenase inhibitor while a derivative, terameprocol, has been trialed as a chemotherapeutic agent. When investigating fatty acid activation of the human transient receptor potential cation channel subfamily A, member 1 (hTRPA1), we found that NDGA activated the channel. Here we investigate the actions of NDGA and terameprocol at hTRPA1 and the consequences of this for noxious cold sensitivity in mice. hTRPA1 was stably expressed in HEK 293 cells (HEK 293-TRPA1) and channel activity examined by measuring changes in intracellular calcium ([Ca]i) using a fluorescent dye and activation of membrane currents using patch clamp electrophysiology. The effects of local NDGA and terameprocol application on acetone-induced paw flinching were examined in mice. NDGA (pEC50 of 5.4 ± 0.1, maximum change in fluorescence of 385 ± 30%) and terameprocol (pEC50 4.5 ± 0.2, maximum 550 ± 75%) increased [Ca]i in HEK 293-hTRPA1 cells. NDGA also induced an increase in membrane conductance in HEK 293-hTRPA1 cells. These effects were prevented by the TRPA1 antagonist HC-030031, and were dependent on the presence of Cys621, Cys 641, and Cys 665 in hTRPA1. Neither NDGA nor terameprocol alone produced spontaneous pain behaviors in mice after hind paw injection, but both enhanced responses to acetone. NDGA and terameprocol are efficacious activators of TRPA1. NDGA should be used with care to probe lipoxygenase involvement in nociception while TRPA1 activity should be considered when considering use of these drugs in humans.

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The combination of TRPM8 and TRPA1 expression causes an invasive phenotype in lung cancer

Cited by 53 publications

References 34 publications

Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut

Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Nordihydroguaiaretic acid activates hTRPA1 and modulates behavioral responses to noxious cold in mice

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