TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis

Crottès, David; Lin, Yu-Hsiu T.; Peters, Christian J.; Gilchrist, John; Wiita, Arun P.; Jan, Yuh Nung

doi:10.1073/pnas.1900703116

Cited by 63 publications

(53 citation statements)

References 45 publications

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“…This is the case for KCa3.1 (Jiang et al, 2017), STIM1 (Wang et al, 2019), TRPM8 (Liu et al, 2018), TRPV6 (Song et al, 2018), TMEM16J (Jun et al, 2017), CLIC1 (Lu et al, 2015;Jia et al, 2016), and AQP1/AQP3 (Zou et al, 2019). The same correlation was obtained on gene expression using qPCR for TRPM8 (Du et al, 2018) or TCGA for TRPM2 (Lin et al, 2018) and TMEM16A (Crottes et al, 2019). Furthermore, the mutation status of TRPM2 was also analyzed using Kaplan-Meier in 10 patients out of 159, and the mutated TRPM2 gene revealed a negative correlation with patient survival, compared to patients expressing wildtype TRPM2 (Lin et al, 2018).…”

Section: Prognostic Markers Of Cancer Progression and Aggressivenesssupporting

confidence: 70%

“…This indicates that TMEM16A is involved in EGF-induced PDAC migration and progression, probably through Ca 2+ signaling. In addition, this study investigated the possible role of TMEM16A to classify PDAC patients (Crottes et al, 2019). They found 10 genes involved in EGF-induced TMEM16A-dependent Ca 2+ signaling, which could distinguish neuro-endocrine tumors from other pancreatic cancers.…”

Section: Chloride Channels In Pdacmentioning

confidence: 99%

“…They found 10 genes involved in EGF-induced TMEM16A-dependent Ca 2+ signaling, which could distinguish neuro-endocrine tumors from other pancreatic cancers. In PDAC, these genes formed three clusters with different genetic profiles that could reflect different molecular characterizations (Crottes et al, 2019).…”

Section: Chloride Channels In Pdacmentioning

confidence: 99%

“…Another recent study has performed a database investigation on the expression of TMEM16A and found that mRNA TMEM16A expression is upregulated in pancreatic cancer ( Crottes et al, 2019 ). The authors found that extracellular application of EGF increased [Ca 2+ ] i and the outward-rectifying Cl - current, which were both inhibited by different TMEM16A inhibitors.…”

Section: Expression Of Ion Channels In Pdac Cells and Human Tissuesmentioning

confidence: 99%

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Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancerrelated deaths in United States and Europe. It is predicted that PDAC will become the second leading cause of cancer-related deaths during the next decades. The development of PDAC is not well understood, however, studies have shown that dysregulated exocrine pancreatic fluid secretion can contribute to pathologies of exocrine pancreas, including PDAC. The major roles of healthy exocrine pancreatic tissue are secretion of enzymes and bicarbonate rich fluid, where ion channels participate to fine-tune these biological processes. It is well known that ion channels located in the plasma membrane regulate multiple cellular functions and are involved in the communication between extracellular events and intracellular signaling pathways and can function as signal transducers themselves. Hereby, they contribute to maintain resting membrane potential, electrical signaling in excitable cells, and ion homeostasis. Despite their contribution to basic cellular processes, ion channels are also involved in the malignant transformation from a normal to a malignant phenotype. Aberrant expression and activity of ion channels have an impact on essentially all hallmarks of cancer defined as; uncontrolled proliferation, evasion of apoptosis, sustained angiogenesis and promotion of invasion and migration. Research indicates that certain ion channels are involved in the aberrant tumor growth and metastatic processes of PDAC. The purpose of this review is to summarize the important expression, localization, and function of ion channels in normal exocrine pancreatic tissue and how they are involved in PDAC progression and development. As ion channels are suggested to be potential targets of treatment they are furthermore suggested to be biomarkers of different cancers. Therefore, we describe the importance of ion channels in PDAC as markers of diagnosis and clinical factors.

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Section: Prognostic Markers Of Cancer Progression and Aggressivenesssupporting

confidence: 70%

Section: Chloride Channels In Pdacmentioning

confidence: 99%

Section: Chloride Channels In Pdacmentioning

confidence: 99%

Section: Expression Of Ion Channels In Pdac Cells and Human Tissuesmentioning

confidence: 99%

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Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

et al. 2020

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“…ANO1-mediated CaCC can be also induced by non-GPCR agonists. For example, the receptor tyrosine kinase (RTK) ligand EGF stimulated a transient calcium response and activated CaCC in the pancreatic cancer cell line AsPC-1, which was inhibited by ANO1 knockdown ( Crottes et al, 2019 ). Likewise, brain-derived neurotrophic factor (BDNF), acting through tropomyosin-related kinase (Trk) receptors ( Binder and Scharfman, 2004 ), induced robust Cl – currents, and these effects were blocked by pharmacological inhibition of ANO1 or by ANO1 knockout ( Hong et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling

Dulin

2020

Front. Physiol.

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Anoctamin-1 (ANO1), also known as TMEM16A, is the most studied member of anoctamin family of calcium-activated chloride channels with diverse cellular functions. ANO1 controls multiple cell functions including cell proliferation, survival, migration, contraction, secretion, and neuronal excitation. This review summarizes the current knowledge of the cellular mechanisms governing the regulation of ANO1 expression and of ANO1-mediated intracellular signaling. This includes the stimuli and mechanisms controlling ANO1 expression, agonists and processes that activate ANO1, and signal transduction mediated by ANO1. The major conclusion is that this field is poorly understood, remains highly controversial, and requires extensive and rigorous further investigation.

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BEST1 Positive Monocytes in Circulation: Visualize Intratumoral Crosstalk between Cancer Cells and Monocytes

Zhang

Wang

et al. 2023

Advanced Science

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Head and neck squamous cell carcinomas (HNSCCs) are characterized by an abundance of monocytes and macrophages recruited from the peripheral blood. However, it has not been determined whether these infiltrated cells can be released back into circulation with a tumor-associated neobiosignature. This study reports that Bestrophin1 (BEST1), a component protein of Ca 2+ -activated Cl − channels (CaCCs), is highly expressed on classical monocytes in the peripheral blood of HNSCC patients. This is due to monocyte education by tumor cells, in which tumoral VEGF-A upregulates BEST1 expression on monocytes through the MEK-ERK-ELK1 pathway. This leads to improved secretion of IL-6 and IL-8, which promotes tumor cell proliferation. This work also finds that BEST1 facilitates the motility of monocytes, contributing to the migration of these cells back into circulation. These results suggest that the expression of BEST1 on peripheral monocytes may be a potential tool for monitoring tumor progression, and opens up the possibility of searching for cancer biomarkers on monocytes rather than on the tumor or its products.

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TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis

Cited by 63 publications

References 45 publications

Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling

BEST1 Positive Monocytes in Circulation: Visualize Intratumoral Crosstalk between Cancer Cells and Monocytes

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