SOX17 and PAX8 constitute an actionable lineage-survival transcriptional complex in ovarian cancer

Lin, Lifeng; Shi, Kaixuan; Zhou, Shaoqing; Cai, Mei-Chun; Zhang, Caiyan; Sun, Yunheng; Zang, Jingyu; Cheng, Lin; Ye, Kaiyan; Ma, Ping; Shen, Peiye; Zhang, Meiying; Cheng, Yan; Qi, Chunting; Liu, Ying; Yin, Xiang; Zheng, Yiyan; Li, Tan; Zhuang, Guanglei; Zang, Rongyu

doi:10.1038/s41388-022-02210-3

Cited by 14 publications

(14 citation statements)

References 50 publications

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“…Nowadays, it is clear that strategies aimed at reducing PAX8 levels or inhibiting binding to crucial interacting proteins may impair tumor progression and modulate the aggressive properties of cancer cells. As already cited, SOX17 functions as driving-tumor MTF together with PAX8 68 ; along the same line Lin et al 75 showed that both transcription factors display Müllerian lineage-specific co-expression and co-regulate a broad range of downstream genes, including those involved in cell cycle and tissue morphogenesis. Moreover, they uncover that transcriptional CDK inhibitors efficiently reduce SOX17 and PAX8 protein levels and also putative PAX8 regulon genes was appreciably abolished.…”

Section: Pax8 As a Target For Ovarian Cancer Therapymentioning

confidence: 62%

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: Pax8 As a Target For Ovarian Cancer Therapymentioning

confidence: 62%

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

Palma¹,

Zannini²

2022

OTT

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“…It would be interesting to know if these compounds regulate interaction of PAX8 with its co-regulators such as p53, SOX17, MECOM or TEAD and drive ovarian cancer progression. Previous studies have identified histone deacetylase (HDAC) inhibitors and CDK12/13 inhibitors to downregulate PAX8 expression leading to tumor reduction [39] , [47] . In this study, we identified losartan and captopril as novel PAX8 inhibitors and demonstrated that these inhibitors regulate PAX8 mediated secretion of fibronectin, cell invasion and tumor spheroid integrity.…”

Section: Discussionmentioning

confidence: 99%

PAX8 modulates the tumor microenvironment of high grade serous ovarian cancer through changes in the secretome

Salvi¹,

Hardy²,

Heath³

et al. 2023

Neoplasia

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“…A recent study suggests that PAX8 has a pro-angiogenic role in HGSCs via its interaction with another developmental factor, SOX17. PAX8 and SOX17 are co-expressed in ovarian cancer cells [126] and together inhibit the expression of SERPINE1, an anti-angiogenic factor, thereby promoting angiogenesis [18]. The PAX8 and SOX17 complex was also shown to regulate other genes involved in the cell cycle and morphogenesis.…”

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

confidence: 99%

“…The PAX8 and SOX17 complex was also shown to regulate other genes involved in the cell cycle and morphogenesis. Interestingly, PAX8 and SOX17 were shown to be co-regulated by CDK12/13, and biochemical inhibition of CDK12/13 downregulates the expression of both proteins [126]. Another work has shown that PAX8 cooperates with PRDM3 (the protein product of the MECOM genomic locus) to regulate genes that are involved in adhesion and the extracellular matrix [127].…”

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

confidence: 99%

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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SOX17 and PAX8 constitute an actionable lineage-survival transcriptional complex in ovarian cancer

Cited by 14 publications

References 50 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

PAX8 modulates the tumor microenvironment of high grade serous ovarian cancer through changes in the secretome

PAX8 in the Junction between Development and Tumorigenesis

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