Carbonic Anhydrase Ix Inhibitors in Cancer Therapy: An Update

Supuran, Claudiu T.; Winum, Jean‐Yves

doi:10.4155/fmc.15.71

Cited by 146 publications

(116 citation statements)

References 36 publications

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“…CA9 is a powerful marker used to diagnose various types of metastatic cancers, including cervical, renal, breast and head, and neck tumors. Preclinical studies in cultured cells have clearly demonstrated that CA9 stimulates the metastatic properties of cancer cells . CA9 expression is increased in EC tissues and is correlated with poor prognosis and a malignant phenotype in patients with ESCC .…”

Section: Discussionmentioning

confidence: 99%

“…Preclinical studies in cultured cells have clearly demonstrated that CA9 stimulates the metastatic properties of cancer cells. 17,18,19 CA9 expression is increased in EC tissues and is correlated with poor prognosis and a malignant phenotype in patients with ESCC. 19 The current study detected increased CA9 expression in PADI4-overexpressing ECA109 cells and in PADI4-overexpressing mouse tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

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PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up‐regulates CA9 expression

Liu

Tang

et al. 2018

Molecular Carcinogenesis

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An increasing amount of evidence indicates that peptidylarginine deiminase isoform 4 (PADI4) plays an important role in tumorigenesis. However, the effects of PADI4 on tumor‐bearing mice are unknown, and no studies have investigated this tumorigenic pathway in an animal model. In the present study, ECA109 cells originating from esophageal squamous cell carcinoma (ESCC) were transfected with PADI4‐expressing lentivirus and were injected into BALB/c nude mice. Tumor size and weight were significantly increased in the mouse tumors established with PADI4‐overexpressing ECA109 cells. PCR array analysis revealed increased CA9 expression in ECA109 cells transfected with a PADI4‐expressing plasmid, while decreased CA9 expression levels were detected in cells transfected with anti‐PADI4 siRNA. Furthermore, up‐regulation of CA9 expression was detected in mouse tumors established with PADI4‐overexpressing cells. Immunohistochemistry detected the increased expression and co‐localization of PADI4 and CA9 in ESCC tissues compared with adjacent non‐tumor tissues and normal tissue controls. These results were verified using Western blotting. Cell proliferation significantly increased or decreased in ECA109 and EC9706 (another ESCC‐originating cell line) cells transfected with a PADI4‐expressing plasmid or anti‐PADI4 siRNA, respectively. The above findings suggest that increased PADI4 expression in ESCC stimulates tumor growth and up‐regulates CA9 expression, which is known to promote metastatic properties in tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up‐regulates CA9 expression

Liu

Tang

et al. 2018

Molecular Carcinogenesis

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“…While the elevation in Ca14 was observed using the C-terminal tagged construct, the tag could not be detected, suggesting cleavage of the C-terminal region. CA9 has been an important target for pH modulation in several cancers including melanoma [45]. Melanosomal fractions from B16 cells did not contain CA14 ( Fig EV3G).…”

Section: Ca14 Is Localized To the Nucleus In Melanocytesmentioning

confidence: 97%

pH‐controlled histone acetylation amplifies melanocyte differentiation downstream of MITF

et al. 2019

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Tanning response and melanocyte differentiation are mediated by the central transcription factor MITF. This involves the rapid and selective induction of melanocyte maturation genes, while concomitantly the expression of other effector genes is maintained. In this study, using cell-based and zebrafish model systems, we report on a pH-mediated feed-forward mechanism of epigenetic regulation that enables selective amplification of the melanocyte maturation program. We demonstrate that MITF activation directly elevates the expression of the enzyme carbonic anhydrase 14 (CA14). Nuclear localization of CA14 leads to an increase of the intracellular pH, resulting in the activation of the histone acetyl transferase p300/CBP. In turn, enhanced H3K27 histone acetylation at selected differentiation genes facilitates their amplified expression via MITF. CRISPR-mediated targeted missense mutation of CA14 in zebrafish results in the formation of immature acidic melanocytes with decreased pigmentation, establishing a central role for this mechanism during melanocyte differentiation in vivo. Thus, we describe an epigenetic control system via pH modulation that reinforces cell fate determination by altering chromatin dynamics.

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“…Carbon dioxide (CO 2 ) and its hydration product bicarbonate (HCO À 3 ) are substrates and products of various metabolic reactions in the cells of different living organisms [1][2][3][4][5][6][7] . CO 2 is the final product of the respiration in all domains of life, from microorganisms to mammals [8][9][10] ; bicarbonate (HCO À 3 ) is a substrate for several carboxylating enzymes involved in biosynthetic pathways such as biosynthesis of fatty acids, amino acids and nucleotides [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

A new procedure for the cloning, expression and purification of the β-carbonic anhydrase from the pathogenic yeastMalassezia globosa, an anti-dandruff drug target

Prete

Luca

Vullo

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Malassezia yeasts are almost exclusively the single eukaryotic members of the fungal flora of the skin. Malassezia globosa and Malassezia restricta are found on the skin of practically all humans. Malassezia globosa is highly implicated in the pathogenesis of dandruff and its genome encodes for only one carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the b-class (MgCA). It has been indeed demonstrated that in many pathogenic microorganisms, CAs are essential for their life cycle and their inhibition can lead to growth impairment and defects. In the previous work, the recombinant MgCA was investigated for its inhibition profile with sulfonamides, which in models of dandruff infection were able to protect animals from the fungal infection, allowing us to propose this enzyme as a new antidandruff target. MgCA was cloned as GST-fusion protein, but the yield was rather low and the protein was often found in inclusion bodies. Here, we propose an alternative procedure consisting in cloning the recombinant MgCA as His-Tag fusion protein. This procedure resulted in a good method to express and purify the active recombinant MgCA, and the protein recovery was better with respect to that used for preparing MG-CA (b-CA cloned as GST-fusion protein).

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Carbonic Anhydrase Ix Inhibitors in Cancer Therapy: An Update

Cited by 146 publications

References 36 publications

PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up‐regulates CA9 expression

PADI4 stimulates esophageal squamous cell carcinoma tumor growth and up‐regulates CA9 expression

pH‐controlled histone acetylation amplifies melanocyte differentiation downstream of MITF

A new procedure for the cloning, expression and purification of the β-carbonic anhydrase from the pathogenic yeastMalassezia globosa, an anti-dandruff drug target

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