CLIC5: a novel ETV6 target gene in childhood acute lymphoblastic leukemia

Neveu, Benjamin; Spinella, Jean-François; Richer, Chantal; Lagacé, Karine; Cassart, Pauline; Lajoie, Mathieu; Jananji, Silvana; Drouin, Simon; Healy, Jasmine; Hickson, Gilles R.X.; Sinnett, Daniel

doi:10.3324/haematol.2016.149740

Cited by 23 publications

(57 citation statements)

References 50 publications

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“…The presence of other IAA94sensitive member of the CLIC family (namely CLIC5A, ref. 36) in GB CSCs was excluded by qRT-PCR and thus confirms the specificity of above results ( Supplementary Fig. S3).…”

Section: Membrane Localization Of Clic1 In S Phasesupporting

confidence: 87%

Mutual Influence of ROS, pH, and CLIC1 Membrane Protein in the Regulation of G1–S Phase Progression in Human Glioblastoma Stem Cells

Peretti

Raciti

Carlini

et al. 2018

Molecular Cancer Therapeutics

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Glioblastoma (GB) is the most lethal, aggressive, and diffuse brain tumor. The main challenge for successful treatment is targeting the cancer stem cell (CSC) subpopulation responsible for tumor origin, progression, and recurrence. Chloride Intracellular Channel 1 (CLIC1), highly expressed in CSCs, is constitutively present in the plasma membrane where it is associated with chloride ion permeability. , CLIC1 inhibition leads to a significant arrest of GB CSCs in G phase of the cell cycle. Furthermore, CLIC1 knockdown impairs tumor growth Here, we demonstrate that CLIC1 membrane localization and function is specific for GB CSCs. Mesenchymal stem cells (MSC) do not show CLIC1-associated chloride permeability, and inhibition of CLIC1 protein function has no influence on MSC cell-cycle progression. Investigation of the basic functions of GB CSCs reveals a constitutive state of oxidative stress and cytoplasmic alkalinization compared with MSCs. Both intracellular oxidation and cytoplasmic pH changes have been reported to affect CLIC1 membrane functional expression. We now report that in CSCs these three elements are temporally linked during CSC G-S transition. Impeding CLIC1-mediated chloride current prevents both intracellular ROS accumulation and pH changes. CLIC1 membrane functional impairment results in GB CSCs resetting from an allostatic tumorigenic condition to a homeostatic steady state. In contrast, inhibiting NADPH oxidase and NHE1 proton pump results in cell death of both GB CSCs and MSCs. Our results show that CLIC1 membrane protein is crucial and specific for GB CSC proliferation, and is a promising pharmacologic target for successful brain tumor therapies. .

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Section: Membrane Localization Of Clic1 In S Phasesupporting

confidence: 87%

Mutual Influence of ROS, pH, and CLIC1 Membrane Protein in the Regulation of G1–S Phase Progression in Human Glioblastoma Stem Cells

Peretti

Raciti

Carlini

et al. 2018

Molecular Cancer Therapeutics

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“…CLIC5 is also expressed along with Ezrin and Podocalyxin in hepatocellular carcinoma participating in the invasion and migration of tumors (Flores-Tellez et al, 2015). CLIC5 is overexpressed in childhood acute lymphoblastic leukemia, following the loss of ETV6 (Neveu et al, 2016). Similar to CLIC4, CLIC5 was also reported in mitochondria where it plays a role in modulation of ROS, which could also contribute to tumor signaling.…”

Section: Clic5 and Clic6mentioning

confidence: 99%

Intracellular Chloride Channels: Novel Biomarkers in Diseases

2020

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“…4 In ETV6-RUNX1 + BCP-ALL, one allele of ETV6 is inactivated by fusion with RUNX1, while the other is often inactivated as well. The WBP1L gene is a target gene of ETV6, which suppresses its expression.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] In general, ETV6 targets are of high interest because of critical importance of ETV6 in haematopoiesis and its involvement in leukaemia. [4][5][6] In general, ETV6 targets are of high interest because of critical importance of ETV6 in haematopoiesis and its involvement in leukaemia.…”

Section: Introductionmentioning

confidence: 99%

“…ETV6, a fusion partner in ETV6-RUNX1, is a transcriptional repressor and WBP1L is one of its target genes. [4][5][6] In general, ETV6 targets are of high interest because of critical importance of ETV6 in haematopoiesis and its involvement in leukaemia. Around 30 fusions of ETV6 to different partner genes and a number of mutations in ETV6 have been identified so far, many of them implicated in various haematological malignancies of myeloid and lymphoid origin.…”

Section: Introductionmentioning

confidence: 99%

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Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

Borna

Drobek

Králová

et al. 2019

J Cellular Molecular Medi

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WW domain binding protein 1-like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6-RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non-haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4-family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l-deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis. | 1981BORNA et Al.

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CLIC5: a novel ETV6 target gene in childhood acute lymphoblastic leukemia

Cited by 23 publications

References 50 publications

Mutual Influence of ROS, pH, and CLIC1 Membrane Protein in the Regulation of G1–S Phase Progression in Human Glioblastoma Stem Cells

Mutual Influence of ROS, pH, and CLIC1 Membrane Protein in the Regulation of G1–S Phase Progression in Human Glioblastoma Stem Cells

Intracellular Chloride Channels: Novel Biomarkers in Diseases

Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

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