Background: Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to the formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive the development of many tumours, limited data exist on ES. This work therefore aimed to study the transcriptional regulation of KCNA2 and define the involvement of the Kv1.
View Article and Find Full Text PDFEwing sarcoma (ES) is characterized by EWS::FLI1 or EWS::ERG fusion proteins. Knowing that ion channels are involved in tumorigenesis, this work aimed to study the involvement of the KCNN1 gene, which encodes the SK1 potassium channel, in ES development. Bioinformatics analyses from databases were used to study KCNN1 expression in patients and cell lines.
View Article and Find Full Text PDFThe mitochondrial Ca2+ uniporter (MCU) plays crucial role in intramitochondrial Ca2+ uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated.
View Article and Find Full Text PDFBackground And Aims: Bevacizumab-based chemotherapy is a recommended first-line treatment for metastatic colorectal cancer (mCRC). Robust biomarkers with clinical practice applicability have not been identified for patients with this treatment. We aimed to evaluate the prognostic yield of serum mid-infrared spectroscopy (MIRS) on patients receiving first-line bevacizumab-based chemotherapy for mCRC.
View Article and Find Full Text PDFRapid Commun Mass Spectrom
October 2024
Rationale: Natural variations in the abundance of the stable isotopes of nitrogen (δN) and carbon (δC) offer valuable insights into metabolic fluxes. In the wake of strong interest in cancer metabolism, recent research has revealed δN and δC variations in cancerous compared to non-cancerous tissues and cell lines. However, our understanding of natural isotopic variations in cultured mammalian cells, particularly in relation to metabolism, remains limited.
View Article and Find Full Text PDFSK3 channels are potassium channels found to promote tumor aggressiveness. We have previously demonstrated that SK3 is regulated by synthetic ether lipids, but the role of endogenous ether lipids is unknown. Here, we have studied the role of endogenous alkyl- and alkenyl-ether lipids on SK3 channels and on the biology of cancer cells.
View Article and Find Full Text PDFMetastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a kinome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and upregulation of the sodium/calcium (Na /Ca ) exchanger SLC8A1.
View Article and Find Full Text PDFIon channels are transmembrane structures that allow the passage of ions across cell membranes such as the plasma membrane or the membranes of various organelles like the nucleus, endoplasmic reticulum, Golgi apparatus or mitochondria. Aberrant expression of various ion channels has been demonstrated in several tumor cells, leading to the promotion of key functions in tumor development, such as cell proliferation, resistance to apoptosis, angiogenesis, invasion and metastasis. The link between ion channels and these key biological functions that promote tumor development has led to the classification of cancers as oncochannelopathies.
View Article and Find Full Text PDFProstate cancer (PCa) represents one of the most frequent diagnosed cancer in males worldwide. Due to routine screening tests and the efficiency of available treatments, PCa-related deaths have significantly decreased over the past decades. However, PCa remains a critical threat if detected at a late stage in which, cancer cells would have already detached from the primary tumor to spread and invade other parts of the body.
View Article and Find Full Text PDFInnate and acquired resistances to therapeutic agents are responsible for the failure of cancer treatments. Due to the multifactorial nature of resistance, the identification of new therapeutic targets is required to improve cancer treatment. Calcium is a universal second messenger that regulates many cellular functions such as proliferation, migration, and survival.
View Article and Find Full Text PDFBackground And Aims: Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of colorectal cancer (CRC). To overcome treatment resistance, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new inhibitor of NCLX.
View Article and Find Full Text PDFTherapeutic strategies for metastatic castration-resistant prostate cancer aim to target androgen receptor signaling. Despite initial survival benefits, treatment resistance invariably occurs, leading to lethal disease. Therapies targeting the androgen receptor can induce the emergence of a neuroendocrine phenotype and reactivate embryonic programs associated with epithelial to mesenchymal transition.
View Article and Find Full Text PDFResistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (CRC) is frequent and prognostic biomarkers are lacking. MicroRNAs (miR) are good candidates in this context. We aimed to characterize cetuximab and panitumumab exposure influence on miR expression in colorectal cancer cells to identify those regulating the EGFR pathway and implicated in resistance to treatment.
View Article and Find Full Text PDFThe modulation of SK3 ion channels can be efficiently and selectively achieved by using the amphiphilic compound Ohmline (a glyco-glycero-ether-lipid). We report herein a series of Ohmline analogues featuring the replacement of one ether function by a thioether function located at the same position or shifted close to its initial position. The variation of the lipid chain length and the preparation of two analogues featuring either one sulfoxide or one sulfone moiety complete this series.
View Article and Find Full Text PDFBackground: Colorectal cancer (CRC) metastases are the main cause of CRC mortality. Intracellular Ca2+ regulates cell migration and invasion, key factors for metastases. Ca2+ also activates Ca2+-dependent potassium channels which in turn affect Ca2+ driving force.
View Article and Find Full Text PDFDespite the established role of mitochondria in cancer, the mechanisms by which mitochondrial Ca (mtCa) regulates tumorigenesis remain incompletely understood. The crucial role of mtCa in tumorigenesis is highlighted by altered expression of proteins mediating mtCa uptake and extrusion in cancer. Here, we demonstrate decreased expression of the mitochondrial Na/Ca/Li exchanger NCLX () in human colorectal tumors and its association with advanced-stage disease in patients.
View Article and Find Full Text PDFRev Physiol Biochem Pharmacol
May 2022
The intracellular Ca concentration is mainly controlled by Ca channels. These channels form complexes with K channels, which function to amplify Ca flux. In cancer cells, voltage-gated/voltage-dependent Ca channels and non-voltage-gated/voltage-independent Ca channels have been reported to interact with K channels such as Ca-activated K channels and voltage-gated K channels.
View Article and Find Full Text PDFHypoxia is a well-established feature of prostate cancer (PCa) and is associated with disease aggressiveness. The hypoxic microenvironment initiates multiple adaptive responses including epithelial-to-mesenchymal transition (EMT) and a remodeling of calcium homeostasis involved in cancer progression. In the present study, we identified a new hypoxia signaling pathway with a positive feedback loop between the EMT transcription factor Zeb1 and SK3, a Ca-activated K+ channel, which leads to amplifying store-operated Ca entry.
View Article and Find Full Text PDFORAI1 constitutes the store-operated Ca release-activated Ca (CRAC) channel crucial for life. Whereas ORAI1 activation by Ca-sensing STIM proteins is known, still obscure is how ORAI1 is turned off through Ca-dependent inactivation (CDI), protecting against Ca toxicity. Here we identify a spatially-restricted Ca/cAMP signaling crosstalk critical for mediating CDI.
View Article and Find Full Text PDF: Colorectal cancer (CRC) is a highly devastating cancer. Ca-dependent channels are now considered key regulators of tumor progression. In this study, we aimed to investigate the association of non-voltage gated Ca channels and Ca-dependent potassium channels (KCa) with CRC using the transcriptional profile of their genes.
View Article and Find Full Text PDFStore-operated Ca entry (SOCE) is a ubiquitous pathway for Ca influx across the plasma membrane (PM). SOCE is mediated by the endoplasmic reticulum (ER)-associated Ca-sensing proteins stromal interaction molecule 1 (STIM1) and STIM2, which transition into an active conformation in response to ER Ca store depletion, thereby interacting with and gating PM-associated ORAI1 channels. Although structurally homologous, STIM1 and STIM2 generate distinct Ca signatures in response to varying strengths of agonist stimulation.
View Article and Find Full Text PDF