Emerging roles for multifunctional ion channel auxiliary subunits in cancer

Haworth, Alexander; Brackenbury, William J.

doi:10.1016/j.ceca.2019.04.005

Cited by 34 publications

(21 citation statements)

References 331 publications

(468 reference statements)

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“…Firstly, our findings are fully in line with the existing studies proposing that tumor acidosis can promote cancer invasiveness. This includes the prominent pattern of upregulation by acidosis of genes involved in ECM remodeling and invasiveness, as well as the striking extent of upregulation of ASIC1, the ENAC α subunit, and other cation channel genes, many of which have been assigned important roles in cell–cell adhesion and invasion [ 60 , 61 ]. Second, our analyses also support several existing studies that clearly show that adaptation to acidosis is not associated with increased growth of the cancer cells [ 13 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Cancer Cell Acid Adaptation Gene Expression Response Is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival

Yao

Czaplińska

Ialchina

et al. 2020

Cancers

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The acidic pH of the tumor microenvironment plays a critical role in driving cancer development toward a more aggressive phenotype, but the underlying mechanisms are unclear. To this end, phenotypic and genotypic changes induced by adaptation of cancer cells to chronic acidosis have been studied. However, the generality of acid adaptation patterns across cell models and their correlation to the molecular phenotypes and aggressiveness of human cancers are essentially unknown. Here, we define an acid adaptation expression response shared across three cancer cell models, dominated by metabolic rewiring, extracellular matrix remodeling, and altered cell cycle regulation and DNA damage response. We find that many genes which are upregulated by acid adaptation are significantly correlated to patient survival, and more generally, that there are clear correlations between acid adaptation expression response and gene expression change between normal and tumor tissues, for a large subset of cancer patients. Our data support the notion that tumor microenvironment acidity is one of the key factors driving the selection of aggressive cancer cells in human patient tumors, yet it also induces a growth-limiting genotype that likely limits cancer cell growth until the cells are released from acidosis, for instance during invasion.

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Section: Discussionmentioning

confidence: 99%

Cancer Cell Acid Adaptation Gene Expression Response Is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival

Yao

Czaplińska

Ialchina

et al. 2020

Cancers

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“…Moreover, compelling studies point to the emerging role of VGCCs accessory subunits in cancer (Haworth and Brackenbury, 2019). The VGCCs are associated with these non-pore forming subunits that tune the biophysical properties of the channel, including activation, gating kinetics or trafficking to the PM (Dolphin, 2016).…”

Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

Calcium Permeable Channels in Cancer Hallmarks

Tajada¹,

Villalobos²

2020

Front. Pharmacol.

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Cancer, the second cause of death worldwide, is characterized by several common criteria, known as the "cancer hallmarks" such as unrestrained cell proliferation, cell death resistance, angiogenesis, invasion and metastasis. Calcium permeable channels are proteins present in external and internal biological membranes, diffusing Ca 2+ ions down their electrochemical gradient. Numerous physiological functions are mediated by calcium channels, ranging from intracellular calcium homeostasis to sensory transduction. Consequently, calcium channels play important roles in human physiology and it is not a surprise the increasing number of evidences connecting calcium channels disorders with tumor cells growth, survival and migration. Multiple studies suggest that calcium signals are augmented in various cancer cell types, contributing to cancer hallmarks. This review focuses in the role of calcium permeable channels signaling in cancer with special attention to the mechanisms behind the remodeling of the calcium signals. Transient Receptor Potential (TRP) channels and Store Operated Channels (SOC) are the main extracellular Ca 2+ source in the plasma membrane of nonexcitable cells, while inositol trisphosphate receptors (IP 3 R) are the main channels releasing Ca 2+ from the endoplasmic reticulum (ER). Alterations in the function and/or expression of these calcium channels, as wells as, the calcium buffering by mitochondria affect intracellular calcium homeostasis and signaling, contributing to the transformation of normal cells into their tumor counterparts. Several compounds reported to counteract several cancer hallmarks also modulate the activity and/or the expression of these channels including non-steroidal anti-inflammatory drugs (NSAIDs) like sulindac and aspirin, and inhibitors of polyamine biosynthesis, like difluoromethylornithine (DFMO). The possible role of the calcium permeable channels targeted by these compounds in cancer and their action mechanism will be discussed also in the review.

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“…Altered calcium handling has indeed been implicated in cancer and there are many reviews available (Anguita and Villalobo 2018 ; Azimi and Monteith 2016 ; Azimi et al 2014 ; Berchtold and Villalobo 2014 ; Bhargava and Saha 2019 ; Bong and Monteith 2018 ; Busselberg and Florea 2017 ; Chalmers and Monteith 2018 ; Cross et al 2014 ; Cui et al 2017 ; Deliot and Constantin 2015 ; Frisch et al 2019 ; Grimm et al 2018 ; Haworth and Brackenbury 2019 ; Hempel and Trebak 2017 ; Humeau et al 2018 ; Iamshanova et al 2017 ; Kadio et al 2016 ; Kim and Wysolmerski 2016 ; Makena and Rao 2020 ; Maly and Hofmann 2018 ; Marchi and Pinton 2016 ; Martinez-Delgado and Felix 2017 ; Mignen et al 2017 ; Missiroli et al 2017 ; Mo and Yang 2018 ; Monteith et al 2007 ; Monteith et al 2017 ; Orrenius et al 2003 ; Pierro et al 2019 ; Prevarskaya et al 2010 , 2011 ; Ritaine et al 2017 ; Roberts-Thomson et al 2019 ; Sallan et al 2018 ; So et al 2019 ; Sterea and El Hiani 2020 ; Stewart et al 2015 ; Tajbakhsh et al 2018 ; Terrie et al 2019 ; Tsai et al 2015 ; Venkateswaran et al 2018 ; Villalobos et al 2017 ; Xu et al 2018 ), including some excellent breast cancer-focused reviews (Azimi et al 2014 ; Cross et al 2014 ; Lee et al 2006 ; So et al 2019 ; Tajbakhsh et al 2018 ). The data from the literature can be generally categorized into three groups.…”

Section: Calcium Signaling and Cancermentioning

confidence: 99%

Calcium signaling: breast cancer’s approach to manipulation of cellular circuitry

2020

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Calcium is a versatile element that participates in cell signaling for a wide range of cell processes such as death, cell cycle, division, migration, invasion, metabolism, differentiation, autophagy, transcription, and others. Specificity of calcium in each of these processes is achieved through modulation of intracellular calcium concentrations by changing the characteristics (amplitude/frequency modulation) or location (spatial modulation) of the signal. Breast cancer utilizes calcium signaling as an advantage for survival and progression. This review integrates evidence showing that increases in expression of calcium channels, GPCRs, pumps, effectors, and enzymes, as well as resulting intracellular calcium signals, lead to high calcium and/or an elevated calcium- mobilizing capacity necessary for malignant functions such as migratory, invasive, proliferative, tumorigenic, or metastatic capacities.

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Emerging roles for multifunctional ion channel auxiliary subunits in cancer

Abstract: Graphical abstract

Cited by 34 publications

References 331 publications

Cancer Cell Acid Adaptation Gene Expression Response Is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival

Cancer Cell Acid Adaptation Gene Expression Response Is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival

Calcium Permeable Channels in Cancer Hallmarks

Calcium signaling: breast cancer’s approach to manipulation of cellular circuitry

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