Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

Cristofaro, Tiziana de; Palma, Tina Di; Soriano, Amata Amy; Monticelli, Antonella; Affinito, Ornella; Cocozza, Sérgio; Zannini, Mariastella

doi:10.18632/oncotarget.9740

Cited by 21 publications

(17 citation statements)

References 101 publications

(108 reference statements)

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“…PAX8 seems to have little functional effect in the fully differentiated adult fallopian tube, but mediates several tumorigenic effects in HGSC, including proliferation, migration, angiogenesis, and apoptosis [ 65 , 70 , 71 , 72 , 79 ]. Reducing PAX8 levels or disrupting the transcriptional activity of PAX8 may inhibit these pro-cancerous effects while leaving the normal fallopian tube epithelium unaffected.…”

Section: Clinical Strategies To Target Pax2 and Pax8mentioning

confidence: 99%

UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Hardy

Salvi

Burdette

2018

Cancers

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High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

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Section: Clinical Strategies To Target Pax2 and Pax8mentioning

confidence: 99%

UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Hardy

Salvi

Burdette

2018

Cancers

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“…Instead, we created an OVCAR4 clone with heterozygous PAX8 deletion that had a decrease in FOXM1 ( Supplement Figure 2 ). Previously published work examined the transcriptome of ovarian cancer cells with PAX8 alteration 10 , 30 . While RNA-sequencing and transcriptomic analysis provides information about the role of PAX8 as a transcription factor, this method does not elucidate the phenotypic and functional effects of PAX8 in HGSOC.…”

Section: Resultsmentioning

confidence: 99%

“…PAX8 is expressed in 99% of serous tumors and affects tumor cell proliferation, morphology, and survival 5 , 6 , 36 , 37 . Several RNA-sequencing studies have been performed to identify the transcriptional targets of PAX8 that lead to these pro-tumorigenic effects 10 , 11 , 30 . In this study, we present the first mass spectrometry based proteomic analysis of cell lines after PAX8 alteration to obtain a more phenotypic picture of pathways regulated by PAX8.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals a role for PAX8 in peritoneal colonization of high grade serous ovarian cancer that can be targeted with micelle encapsulated thiostrepton

et al. 2019

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High grade serous ovarian cancer (HGSOC) is the fifth leading cause of cancer deaths among women yet effective targeted therapies against this disease are limited. The heterogeneity of HGSOC, including few shared oncogenic drivers and origination from both the fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE), has hampered development of targeted drug therapies. PAX8 is a lineage-specific transcription factor expressed in the FTE that is also ubiquitously expressed in HGSOC where it is an important driver of proliferation, migration, and cell survival. PAX8 is not normally expressed in the OSE, but it is turned on after malignant transformation. In this study, we use proteomic and transcriptomic analysis to examine the role of PAX8 leading to increased migratory capabilities in a human ovarian cancer model, as well as in tumor models derived from the OSE and FTE. We find that PAX8 is a master regulator of migration with unique downstream transcriptional targets that are dependent on the cell’s site of origin. Importantly, we show that targeting PAX8, either through CRISPR genomic alteration or through drug treatment with micelle encapsulated thiostrepton, leads to a reduction in tumor burden. These findings suggest PAX8 is a unifying protein driving metastasis in ovarian tumors that could be developed as an effective drug target to treat HGSOC derived from both the OSE and FTE.

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“…RNA-Seq raw data (SRR3289902), Cristofer, et al [38] was downloaded from the Sequence Read Archive (SRA) (www.ncbi.nlm.nih.gov/geo) in format of Fstaq. The data included three ovarian tumor and three normal samples.…”

Section: Data Processing Methods and Software Sourcesmentioning

confidence: 99%

Gene expression profiles and pathway enrichment analysis to identification of differentially expressed gene and signaling pathways in epithelial ovarian cancer based on high-throughput RNA-seq data

Siavoshi

Taghizadeh

Dookhe

et al. 2019

Preprint

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Epithelial ovarian cancer (EOC) can be considered as a stressful and challenging disease among all women in the world, which has been associated with a poor prognosis and its molecular pathogenesis has remained unclear. In recent years, RNA Sequencing (RNA-seq) has become a functional and amazing technology for profiling gene expression. In the present study, RNA-seq raw data from Sequence Read Archive (SRA) of six tumor and normal ovarian sample was extracted, and then analysis and statistical interpretation was done with Linux and R Packages from the open-source Bioconductor. Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied for the identification of key genes and pathways involved in EOC. We identified 1091 Differential Expression Genes (DEGs) which have been reported in various studies of ovarian cancer as well as other types of cancer. Among them, 333 genes were up-regulated and 273 genes were downregulated. In addition, Differentially Expressed Genes (DEGs) including RPL41, ALDH3A2, ERBB2, MIEN1, RBM25, ATF4, UPF2, DDIT3, HOXB8 and IL17D as well as Ribosome and Glycolysis/Gluconeogenesis pathway have had the potentiality to be used as targets for EOC diagnosis and treatment. In this study, unlike that of any other studies on various cancers, ALDH3A2 was most down-regulated gene in most KEGG pathways, and ATF4 was most up-regulated gene in leucine zipper domain binding term. In the other hand, RPL41 as a regulatory of cellular ATF4 level was up-regulated in many term and pathways and augmentation of ATF4 could justify the increase of RPL41 in the EOC. Pivotal pathways and significant genes, which were identified in the present study, can be used for adaptation of different EOC study. However, further molecular biological experiments and computational processes are required to confirm the function of the identified genes associated with EOC.

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Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

Cited by 21 publications

References 101 publications

UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Proteomic analysis reveals a role for PAX8 in peritoneal colonization of high grade serous ovarian cancer that can be targeted with micelle encapsulated thiostrepton

Gene expression profiles and pathway enrichment analysis to identification of differentially expressed gene and signaling pathways in epithelial ovarian cancer based on high-throughput RNA-seq data

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