ArticleCell death and differentiation2020
Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of lncRNA AK015322 increases sperm morphological abnormalities and impairs motility in mice.Molecular and cellular biochemistry · 2026Article
- miRNA Sequencing and Differential Analysis of Testis in 1-Year-Old and 2-Year-Old Kazakh Horses.Biology · 2026Article
- EM2, a Natural Product MST1/2 Kinase Activator, Suppresses Non-Small Cell Lung Cancer via Hippo Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Testicular heterochrony in vgll3-mediated maturation age in Atlantic salmon.G3 (Bethesda, Md.) · 2025Article
- Inhibition of BRD4 sensitizes NSCLC cells to osimertinib by suppressing APT1 and promoting MST1 palmitoylation.Cell death discovery · 2025Article
- Alterations in the Hippo Signaling Pathway During Adenogenesis Impairment in Postnatal Mouse Uterus.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Molecular Pathways Implicated in the Differentiation and Function of Epididymal Basal Cells.Advances in experimental medicine and biology · 2025Review
- STK3 kinase activation inhibits tumor proliferation through FOXO1-TP53INP1/P21 pathway in esophageal squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- RUNX transcription factors are essential in maintaining epididymal epithelial differentiation.Cellular and molecular life sciences : CMLS · 2024Article
- Essential Regulation of YAP1 in Fate Determinations of Spermatogonial Stem Cells and Male Fertility by Interacting with RAD21 and Targeting NEDD4 in Humans and Mice.Research (Washington, D.C.) · 2024Article
- The potential role of Hippo pathway regulates cellular metabolism via signaling crosstalk in disease-induced macrophage polarization.Frontiers in immunology · 2023Review
- FGF6 promotes cardiac repair after myocardial infarction by inhibiting the Hippo pathway.Cell proliferation · 2022Article
- The Role of Altered Mitochondrial Metabolism in Thyroid Cancer Development and Mitochondria-Targeted Thyroid Cancer Treatment.International journal of molecular sciences · 2021Review
- Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis.Journal of oncology · 2021Article
- Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis.Molecules (Basel, Switzerland) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the roles of the Hippo pathway in organogenesis and tumorigenesis have been well studied in multiple organs, its role in sperm maturation and male fertility has not been investigated. The initial segment (IS) of the epididymis plays a critical role in sperm maturation. IS differentiation is governed by ERK1/2, but the mechanisms of ERK1/2 activation in IS are not fully understood. Here we show that double knockout (dKO) of mammalian sterile 20-like kinases 1 and 2 (Mst1 and Mst2), homologs of Hippo in Drosophila, in the epididymal epithelium led to male infertility in mice. Sperm in the cauda epididymides of mutant mice were immotile with flagellar angulation and severely disorganized structures. Loss of Mst1/2 activated YAP and increased proliferation and cell death in all the segments of epididymis. The mutant mice showed substantially suppressed MEK/ERK signaling in the IS and failed IS differentiation. Deletion of Yap restored the reduced MEK/ERK signaling, and partially rescued the defective IS differentiation and fertility in Mst1/2 dKO mice. Our results demonstrate that YAP inhibits the MEK/ERK pathway in IS epithelial cells, and MST1/2 control IS differentiation and fertility at least partially by repressing YAP. Taken together, the Hippo pathway is essential for sperm maturation and male fertility.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.