Chemotherapy resistance in acute lymphoblastic leukemia requires hERG1 channels and is overcome by hERG1 blockers

Pillozzi, Serena; Masselli, Marika; Lorenzo, Emanuele De; Accordi, Benedetta; Cilia, Emanuele; Crociani, Olivia; Amedei, Amedeo; Veltroni, Marinella; D’Amico, Massimo; Basso, Giuseppe; Becchetti, Andrea; Campana, Dario; Arcangeli, Annarosa

doi:10.1182/blood-2010-01-262691

Cited by 124 publications

(151 citation statements)

References 45 publications

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“…Localized at the apical or basolateral membrane of the cells, ion channels/transporters are in a strategic position to sense and transmit extracellular signals into the intracellular machinery. Often, this transmission is mediated by their direct or indirect interaction with ECM proteins, such as intergrins [34] and laminin [35]. Apart from that, ion channels are readily responsive to various environment stimuli, such as pH and hypoxia.…”

Section: Ion Channels/transporters and Their Crosstalk With The Micromentioning

confidence: 99%

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

Jiang

Zhang

Chan

2012

Sci. China Life Sci.

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MicroRNA (miRNA) alterations in response to changes in an extracellular microenvironment have been observed and considered as one of the major mechanisms for epigenetic modifications of the cell. While enormous efforts have been made in the understanding of the role of miRNAs in regulating cellular responses to the microenvironment, the mechanistic insight into how extracellular signals can be transduced into miRNA alterations in cells is still lacking. Interestingly, recent studies have shown that ion channels/transporters, which are known to conduct or transport ions across the cell membrane, also exhibit changes in levels of expression and activities in response to changes of extracellular microenvironment. More importantly, alterations in expression and function of ion channels/transporters have been shown to result in changes in miRNAs that are known to change in response to alteration of the microenvironment. In this review, we aim to summarize the recent data demonstrating the ability of ion channels/transporters to transduce extracellular signals into miRNA changes and propose a potential link between cells and their microenvironment through ion channels/transporters. At the same time, we hope to provide new insights into epigenetic regulatory mechanisms underlying a number of physiological and pathological processes, including embryo development and cancer metastasis. ion channel, miRNAs, epigenetic, microenvironment

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Section: Ion Channels/transporters and Their Crosstalk With The Micromentioning

confidence: 99%

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

Jiang

Zhang

Chan

2012

Sci. China Life Sci.

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show abstract

“…Indeed, our preliminary data indicate that an inhibitor of MEK/ERK signaling further potentiated the cytotoxic effect of the combined treatment, in agreement with the observation that CXCR4/CXCL12 signaling also controls the MEK/ERK cascade. 45 The difficulty in eradicating tumors might result from the conventional treatments targeting the bulk of the tumor cells, but not the LIC. 46 Therefore, strategies that eliminate these cells could have significant clinical implications.…”

Section: Active Site Mtor Inhibitors In T-all C Evangelisti Et Almentioning

confidence: 99%

Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia

et al. 2011

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“…In vivo, hERG positive blasts are more efficient in invading the peripheral circulation and the extramedullary sites after engraftment into immunodeficient mice (Pillozzi et al, 2007). In acute lymphoblastic leukaemia, hERG expression enhances chemotherapy-induced apoptosis and drug resistance (Pillozzi et al, 2011). In the MDA-MD-435s cell line, hERG participates to cell migration and proliferation through a MAP kinase/c-fos pathway.…”

Section: Voltage-gated Potassium Channel Hergmentioning

confidence: 99%