ArticleMolecular therapy. Nucleic acids2018
PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2026Review
- Comprehensive analysis of zinc finger protein 367 as a potential pan-cancer diagnostic and prognostic biomarker and underlying biological mechanisms.Discover oncology · 2025Article
- Microarray and Single-Cell RNA Sequencing Reveals G-Protein Gene Expression Signatures of Spermatogonia Stem Cell.Stem cell reviews and reports · 2025Article
- The transcriptional regulation of NUPR1 expression by MYC is implicated in the regulation of ferroptosis in human spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2025Article
- Unraveling the Regulatory Function of MicroRNAs in Reproductive System Apoptosis and Their Implications for Infertility.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility.Cell biology and toxicology · 2025Review
- Molecular mechanisms of cellular dysfunction in testes from men with non-obstructive azoospermia.Nature reviews. Urology · 2024Review
- 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
- Article
- A Transcriptional Analysis of Cattle Immune Cells Reveals a Central Role of Type 1 Interferon in the In Vitro Innate Immune Response againstPathogens (Basel, Switzerland) · 2023Article
- Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression.International journal of molecular sciences · 2023Article
- GCNA is a histone binding protein required for spermatogonial stem cell maintenance.Nucleic acids research · 2023Article
- Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation.Biological research · 2023Article
- OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility.Research (Washington, D.C.) · 2023Article
- GPx3 knockdown inhibits the proliferation and DNA synthesis and enhances the early apoptosis of human spermatogonial stem cells via mediating CXCL10 and cyclin B1.Frontiers in cell and developmental biology · 2023Article
- Long non-coding RNA CNALPTC1 promotes gastric cancer progression by regulating the miR-6788-5p/PAK1 pathway.Journal of gastrointestinal oncology · 2022Article
- Article
- Recent insights into the microRNA and long non-coding RNA-mediated regulation of stem cell populations.3 Biotech · 2022Review
- Individual variation in buffalo somatic cell cloning efficiency is related to glycolytic metabolism.Science China. Life sciences · 2022Article
- Regulation of spermatogonial stem cell self-renewal and proliferation in mammals.Histology and histopathology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spermatogonial stem cells (SSCs) have significant applications in reproductive and regenerative medicine. However, nothing is known about genes in mediating human SSCs. Here we have explored for the first time the function and mechanism of P21-activated kinase 1 (PAK1) in regulating the proliferation and apoptosis of the human SSC line. PAK1 level was upregulated by epidermal growth factor (EGF), but not glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF2). PAK1 promoted proliferation and DNA synthesis of the human SSC line, whereas PAK1 suppressed its apoptosis in vitro and in vivo. RNA sequencing identified that PDK1, ZNF367, and KDR levels were downregulated by PAK1 knockdown. Immunoprecipitation and Western blots demonstrated that PAK1 interacted with PDK1. PDK1 and KDR levels were decreased by ZNF367-small interfering RNAs (siRNAs). The proliferation of the human SSC line was reduced by PDK1-, KDR-, and ZNF367-siRNAs, whereas its apoptosis was enhanced by these siRNAs. The levels of phos-ERK1/2, phos-AKT, and cyclin A were decreased by PAK1-siRNAs. Tissue arrays showed that PAK1 level was low in non-obstructive azoospermia patients. Collectively, PAK1 was identified as the first molecule that controls proliferation and apoptosis of the human SSC line through PDK1/KDR/ZNF367 and the ERK1/2 and AKT pathways. This study provides data on novel gene regulation and networks underlying the fate of human SSCs, and it offers new molecular targets for human SSCs in translational medicine.
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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.