ATP2A3 gene is involved in cancer susceptibility

Korošec, Branka; Glavač, Damjan; Volavšek, Metka; Ravnik‐Glavač, Metka

doi:10.1016/j.cancergencyto.2008.10.007

Cited by 30 publications

(25 citation statements)

References 31 publications

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“…Overexpressed BIN2 fusions were detected in myeloproliferative neoplasms [31]. Out of other candidates, ATP2A3 has been shown to be mutated and downregulated in HNSCC, lung, colon and central nervous system cancers [50]. Several polymorphism of CYP1B1 are found in many cancer types, including tobacco-related cancers; CYP1B1 is also overexpressed in ovarian cancer [51, 52].…”

Section: Discussionmentioning

confidence: 99%

Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC

et al. 2017

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Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues. We identified 15 epigenetically regulated candidates by focusing on a subset of the genes with a negative correlation between gene expression and promoter methylation. Differential expression and methylation of 3 selected candidates (BANK1, BIN2, and DTX1) were confirmed in an independent HNSCC cohorts from Johns Hopkins and TCGA (The Cancer Genome Atlas). We further performed functional evaluation of NOTCH regulator, DTX1, which was downregulated by promoter hypermethylation in tumors, and demonstrated that decreased expression of DTX1 in HNSCC tumors maybe associated with NOTCH pathway activation and increased migration potential.

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Section: Discussionmentioning

confidence: 99%

Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC

et al. 2017

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“…Although heterozygous knock-out of the SERCA2 gene leads to squamous tumorigenesis in mice with long incubation times [62], the corresponding human condition, Darier disease [127,128] does not appear to predispose to tumor formation, and SERCA3 knock-out mice don’t display a neoplastic phenotype. On the other hand, SERCA inhibitors such as thapsigargin [129] or 2,5-di- tert -butyl-1,4-benzohydroquinone [130] are known tumor promoters in vivo , and mutations in SERCA2, as well as SERCA3 sequences have been found in several human tumor types [131,132,133]. These observations, when combined with data on SERCA expression in cancers, indicate that ER calcium homeostasis is involved in the establishment of several types of the malignant phenotype.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum Calcium Pumps and Cancer Cell Differentiation

et al. 2012

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The endoplasmic reticulum (ER) is a major intracellular calcium storage pool and a multifunctional organelle that accomplishes several calcium-dependent functions involved in many homeostatic and signaling mechanisms. Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA)-type calcium pumps. SERCA activity can determine ER calcium content available for intra-ER functions and for calcium release into the cytosol, and can shape the spatiotemporal characteristics of calcium signals. SERCA function therefore constitutes an important nodal point in the regulation of cellular calcium homeostasis and signaling, and can exert important effects on cell growth, differentiation and survival. In several cell types such as cells of hematopoietic origin, mammary, gastric and colonic epithelium, SERCA2 and SERCA3-type calcium pumps are simultaneously expressed, and SERCA3 expression levels undergo significant changes during cell differentiation, activation or immortalization. In addition, SERCA3 expression is decreased or lost in several tumor types when compared to the corresponding normal tissue. These observations indicate that ER calcium homeostasis is remodeled during cell differentiation, and may present defects due to decreased SERCA3 expression in tumors. Modulation of the state of differentiation of the ER reflected by SERCA3 expression constitutes an interesting new aspect of cell differentiation and tumor biology.

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“…Mutations in the human ATP2A2 gene affecting SERCA2 lead to Darier syndrome in humans, a dermatological syndrome. 10,11 SERCA mutations are associated with some cancers, [12][13][14] suggesting involvement in cell differentiation. 15 SERCA3 human mutations seem associated with type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%