ArticleCell cycle (Georgetown, Tex.)2015
Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21(Waf1/Cip1) and p27(kip1).
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- AKT Phosphorylation of FOXK2 at Ser398 Impacts Breast Cancer Cell Growth and Viability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Review
- The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials.Stem cell research & therapy · 2025Review
- p21Cancers · 2024Article
- Nuclear MAST4 Suppresses FOXO3 through Interaction with AKT3 and Induces Chemoresistance in Pancreatic Ductal Carcinoma.International journal of molecular sciences · 2024Article
- mTORC2 Is Activated under Hypoxia and Could Support Chronic Myeloid Leukemia Stem Cells.International journal of molecular sciences · 2023Article
- Knockdown of the prognostic cancer stem cell marker Musashi-1 decreases radio-resistance while enhancing apoptosis in hormone receptor-positive breast cancer cells via p21Journal of cancer research and clinical oncology · 2021Article
- Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2.Cell death & disease · 2021Article
- Transmembrane and coiled-coil domain family 3 (TMCC3) regulates breast cancer stem cell and AKT activation.Oncogene · 2021Article
- Morusin inhibits the growth of human colorectal cancer HCT116‑derived sphere‑forming cells via the inactivation of Akt pathway.International journal of molecular medicine · 2021Article
- Review
- Bioinformatics Studies Provide Insight into Possible Target and Mechanisms of Action of Nobiletin against Cancer Stem Cells.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Myosin 1b Regulates Nuclear AKT Activation by Preventing Localization of PTEN in the Nucleus.iScience · 2019Article
- Phosphorylated Progesterone Receptor Isoforms Mediate Opposing Stem Cell and Proliferative Breast Cancer Cell Fates.Endocrinology · 2019Article
- AKT/protein kinase B associates with β-actin in the nucleus of melanoma cells.Bioscience reports · 2019Article
- Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI3K/AKT pathway.Cell proliferation · 2018Article
- Review
- The HDAC Inhibitor Quisinostat (JNJ-26481585) Supresses Hepatocellular Carcinoma alone and Synergistically in Combination with Sorafenib by G0/G1 phase arrest and Apoptosis induction.International journal of biological sciences · 2018Article
- TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway.Journal of Cancer · 2018Article
- New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets.Autophagy · 2017Review
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledCancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44(+High)/CD24(-Low) phenotype. This effect was completely reversed in the presence of Akt-specific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21(Waf1/Cip1) and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. SUMMARY: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.
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