NHE7 drives endometrial cancer progression by delaying senescence through cAMP/CREB/GRIN2B axis-mediated Ca²⁺ influx Article Swipe
Shizhou Yang
,
Tao Shen
,
Minghua Yu
,
Tingting Wu
,
Linhua Qian
,
Wu Liu
,
Ting Wang
,
Xiufeng Huang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08296-1
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08296-1
Endometrial cancer (EC) remains a lethal gynecological malignancy with limited therapeutic options owing to unresolved pathogenesis. Cellular senescence acts as a key barrier against tumorigenesis in cancer cells, thus investigating its role in EC progression represents a pivotal research avenue to address these challenges. This study reveals the critical role of cellular senescence in EC progression through multi-omics profiling and functional validation. The integrative analysis of RNA-seq and clinical datasets identified Na+/H+ exchanger 7 (NHE7) as a prognostic biomarker that was significantly overexpressed in EC tissues. Functional studies demonstrated that NHE7 overexpression drives proliferation, cell motility, and cell cycle progression while suppressing senescence-associated markers and cytokine secretion. Conversely, NHE7 knockdown reversed these oncogenic phenotypes. Mechanistically, NHE7 binds to a cAMP-related transcription factor, thereby increasing GRIN2B expression to elevate intracellular Ca²⁺ levels influx, which delays cell senescence and promotes cancer progression in vitro and in vivo. Our findings suggest that NHE7 plays a crucial role in delaying cellular senescence and advancing EC progression through the cAMP pathway, uncovering critical mechanistic drivers of EC pathogenesis and highlighting actionable therapeutic targets.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s42003-025-08296-1
- https://www.nature.com/articles/s42003-025-08296-1.pdf
- OA Status
- gold
- References
- 68
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411051483
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411051483Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s42003-025-08296-1Digital Object Identifier
- Title
-
NHE7 drives endometrial cancer progression by delaying senescence through cAMP/CREB/GRIN2B axis-mediated Ca²⁺ influxWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-05Full publication date if available
- Authors
-
Shizhou Yang, Tao Shen, Minghua Yu, Tingting Wu, Linhua Qian, Wu Liu, Ting Wang, Xiufeng HuangList of authors in order
- Landing page
-
https://doi.org/10.1038/s42003-025-08296-1Publisher landing page
- PDF URL
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https://www.nature.com/articles/s42003-025-08296-1.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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-
https://www.nature.com/articles/s42003-025-08296-1.pdfDirect OA link when available
- Concepts
-
CREB, Endometrial cancer, Senescence, Endocrinology, Internal medicine, Cancer, Medicine, Cancer research, Biology, Transcription factor, Gene, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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68Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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