PAX8 plays an essential antiapoptotic role in uterine serous papillary cancer

Fares, Basem; Berger, Liron; Bangiev-Girsh, Einav; Kakun, Reli Rachel; Ghannam-Shahbari, Dima; Tabach, Yuval; Zohar, Yaniv; Gottlieb, Eyal; Perets, Ruth

doi:10.1038/s41388-021-01925-z

Cited by 6 publications

(7 citation statements)

References 64 publications

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“…79 Hence, it is reasonable to suppose that its putative targets could have an important role as secretory factors and serve both as suitable biomarkers for the early diagnosis of HGSC and as useful therapeutic target against this malignancy. In parallel, the early evidences on PAX8 involvement in the metabolic reprogramming 54,61 could indicate new candidates in terms of novel targets and predictive biomarkers. In conclusion, we think that the combined therapeutic approaches of PAX inhibitors with other chemotherapeutic drugs may enhance their efficacy and in particular improve the survival of patients with a worse prognosis.…”

Section: Discussionmentioning

confidence: 95%

“… 64 On the contrary, in endometrial carcinoma mutated p53 and cytoplasmic p21 can independently mediate the pro-proliferative role of PAX8. 61 To better understand PAX8 function and to gain new insights on the transcriptional mechanism(s) regulated by PAX8 leading to OC, RNA-seq analysis before and after PAX8 knockdown were performed in Fallopian tube and ovarian cancer cell lines by several research groups. In 2016, our group compared the transcriptome of normal Fallopian tube secretory epithelial cells (FT-194) with that of ovarian cancer cells (SKOV-3) before and after PAX8 silencing, to identify genes and pathways modified during the transformation process and regulated by this transcription factor.…”

Section: Pax8 Mechanism Of Action In Hgscmentioning

confidence: 99%

“…50,[55][56][57] In 2021, numerous and representative studies on PAX8 expression and role in epithelial carcinomas were thoroughly and accurately reviewed by Khizer et al 58 Overall, PAX8 emerges as an important factor for cancer cell growth and viability/survival through transcriptional regulation of key factors such as Bcl2, 59 E2F1, 60 p53 and p21. 61 However, to improve our knowledge on the role of this transcription factor in malignancies, it will be necessary to define the molecular pathways regulated by PAX8 and the multiprotein complexes it is part of in different contexts.…”

Section: Biological Activity Of Pax8 In Cancersmentioning

confidence: 99%

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PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far

Palma¹,

Zannini²

2022

OTT

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The Fallopian tube epithelium harbors the origin cells for the majority of high-grade serous ovarian carcinomas (HGSCs), the most lethal form of gynecologic malignancies. PAX8 belongs to the paired-box gene family of transcription factors and it is a marker of the FTE secretory cell lineage. Its role has been investigated in migration, invasion, proliferation, cell survival, stem cell maintenance, angiogenesis and tumor growth. In this review, we focus on the pro-tumorigenic role of PAX8 in ovarian cancer; in this context, PAX8 possibly continues to exert its transcriptional activity on its physiological targets but may also function on newly available targets after the tumorigenic hits. Acquiring new insights into the different PAX8 mechanism(s) of action in the tumor microenvironment could uncover new viable therapeutic targets and thus improve the current treatment regimen.

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Section: Discussionmentioning

confidence: 95%

Section: Pax8 Mechanism Of Action In Hgscmentioning

confidence: 99%

Section: Biological Activity Of Pax8 In Cancersmentioning

confidence: 99%

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PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far

Palma¹,

Zannini²

2022

OTT

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“…[ 12 ] PAX8 positively regulates mutated p53, and missense p53 mutations have an oncogenic gain of function effect. [ 13 ] The pathogenesis of PAX8 in endometrial cancer patients in this region warrants further study.…”

Section: Discussionmentioning

confidence: 99%

Significance analysis of PAX8 expression in endometrial carcinoma

Huang

Gan²,

Yang

2022

Medicine

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To analyze the expression and prognostic value of paired-box 8 (PAX8) expression in uterine corpus endometrial carcinoma (UCEC) by bioinformatics. The expression of PAX8 gene in UCEC was analyzed by R language and immunohistochemistry. The correlation between PAX8 expression and clinicopathological features was analyzed by R language. The prognostic factors was analyzed by univariate/multivariate regression. The survival curve of patients was analyzed by Kaplan–Meier Plotter (K–M Plotter). The diagnostic value of PAX8 in UCEC was analyzed by receiver operating characteristic curve, and the relationship between PAX8 expression and methylation was analyzed by Ualcan. The relationship between methylation and prognosis was analyzed by MethSurv database. The expression of PAX8 in cancer tissues was significantly higher than that in normal tissues. The expression of PAX8 was related to clinical stage, age, histological type, histologic grade, tumor invasion and disease-specific survival event. Univariate/multivariate regression analysis showed that clinical stage, tumor invasion, and PAX8 expression were the influence factors of overall survival (OS), while histologic grade and PAX8 expression were the influence factors of disease-specific survival, and patients with low expression had a longer OS. The area under the curve of receiver operating characteristic curve was 0.81 for PAX8 diagnosis of UCEC. PAX8 was hypomethylated in cancer tissue, and patients with hypermethylated PAX8 had a longer OS. The high expression of PAX8 induced by hypomethylation may play an important role in the occurrence and prognosis of UCEC.

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“…We have published on the role of PAX8 in an especially aggressive subtype of endometrial cancer, uterine serous papillary carcinoma. We have shown that in uterine serous papillary carcinoma, PAX8 plays a pro-proliferative and anti-apoptotic role that is mediated via transcriptional activation of cytoplasmic p21, which has an antiapoptotic role in this disease [135].…”

Section: The Role Of Pax8 In Tumors Of the Female Genital Systemmentioning

confidence: 96%

PAX8 in the Junction between Development and Tumorigenesis

Kakun

Melamed

Perets

2022

IJMS

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Normal processes of embryonic development and abnormal transformation to cancer have many parallels, and in fact many aberrant cancer cell capabilities are embryonic traits restored in a distorted, unorganized way. Some of these capabilities are cell autonomous, such as proliferation and resisting apoptosis, while others involve a complex interplay with other cells that drives significant changes in neighboring cells. The correlation between embryonic development and cancer is driven by shared proteins. Some embryonic proteins disappear after embryogenesis in adult differentiated cells and are restored in cancer, while others are retained in adult cells, acquiring new functions upon transformation to cancer. Many embryonic factors embraced by cancer cells are transcription factors; some are master regulators that play a major role in determining cell fate. The paired box (PAX) domain family of developmental transcription factors includes nine members involved in differentiation of various organs. All paired box domain proteins are involved in different cancer types carrying pro-tumorigenic or anti-tumorigenic roles. This review focuses on PAX8, a master regulator of transcription in embryonic development of the thyroid, kidney, and male and female genital tracts. We detail the role of PAX8 in each of these organ systems, describe its role during development and in the adult if known, and highlight its pro-tumorigenic role in cancers that emerge from PAX8 expressing organs.

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PAX8 plays an essential antiapoptotic role in uterine serous papillary cancer

Cited by 6 publications

References 64 publications

PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far

PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far

Significance analysis of PAX8 expression in endometrial carcinoma

PAX8 in the Junction between Development and Tumorigenesis

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