Cell Proliferation最新文献

Pathological observations show that cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration. However, general principles governing collective cell migration remain to be discovered. Different from individual cell migration, we demonstrated that the Notch-1-activation reduced collective cells speed and distances. In particular, Notch-1-activation induced cellular cytoskeletal remodelling, strengthened the intercellular junctions and cell-matrix adhesions. Mechanistically, Notch-1 activation prevented the phosphorylation of GSK-3β and the translocation of cytoplasmic free β-catenin to the nucleus, which increased E-cadherin expression and tight intercellular junctions. Moreover, Notch-1 signalling also activated the RhoA/ROCK pathway, promoting reorganization of F-actin and contractile forces produced by myosin. Further, Notch-1 activation increased cell adhesion to the extracellular substrate, which inhibited collective cell migration. These findings highlight that cell adhesions and cell-cell junctions contribute to collective cell migration and provide new insights into mechanisms of the modulation of Notch-1 signalling pathway on cancer cell malignancy.

Aromatase inhibitors are effective in treating hormone receptor-positive breast cancer, particularly in postmenopausal women. However, the challenges of inconsistent dissolution, variable absorption and side effects with oral administration persist. To address these issues, transdermal delivery has emerged as a viable alternative. In our study, we have developed nanoemulsion-based transdermal creams containing third-generation aromatase inhibitors Exemestane (EXE) or Letrozole (LE) and evaluated their toxicity, anti-tumour effects and androgenic potency using preclinical models including Bama minipigs, DMBA-induced breast cancer rats and orchidectomized male rats. The results of our study are significant, suggesting that both creams effectively penetrated the skin, demonstrating an impressive anti-breast cancer effect. Importantly, EXE cream had no organ toxicity at the tested dose, providing a reassuring safety profile for its use. In contrast, LE cream displayed reversible toxicity from drug molecule itself in animals at the given dose, dissipating after 3 weeks of withdrawal and recovery. This study establishes a solid foundation for the safe clinical use of third-generation aromatase inhibitors. It highlights transdermal creams as a promising drug delivery carrier for administering them.

The transition from fetal primordial germ cells (PGCs) to spermatogonia (SPG) is critical for male germ cell development; however, the detailed transcriptomic dynamics and regulation underlying this transition remain poorly understood. Here by interrogating the comprehensive transcriptome atlas dataset of mouse male germ cells and gonadal cells development, we elucidated the regulatory networks underlying this transition. Our single-cell transcriptome analysis revealed that the transition from PGCs to SPG was characterized by global hypertranscription. A total of 315 highly active regulators were identified to be potentially involved in this transition, among which a non-transcription factor (TF) regulator TAGLN2 was validated to be essential for spermatogonial stem cells (SSCs) maintenance and differentiation. Metabolism profiling analysis also revealed dynamic changes in metabolism-related gene expression during PGC to SPG transition. Furthermore, we uncovered that intricate cell-cell communication exerted potential functions in the regulation of hypertranscription in germ cells by collaborating with stage-specific active regulators. Collectively, our work extends the understanding of molecular mechanisms underlying male germ cell development, offering insights into the recapitulation of germ cell generation in vitro.

Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) and plays a crucial role in neurological diseases. The process involves a series of steps, including NSC proliferation, migration and differentiation, which are regulated by multiple pathways such as neurotrophic Trk and fibroblast growth factor receptors (FGFR) signalling. Despite the discovery of numerous compounds capable of modulating individual stages of neurogenesis, it remains challenging to identify an agent that can regulate multiple cellular processes of neurogenesis. Here, through screening of bioactive compounds in dietary functional foods, we identified a flavonoid chrysin that not only enhanced the human NSCs proliferation but also facilitated neuronal differentiation and neurite outgrowth. Further mechanistic study revealed the effect of chrysin was attenuated by inhibition of neurotrophic tropomyosin receptor kinase-B (TrkB) receptor. Consistently, chrysin activated TrkB and downstream ERK1/2 and AKT. Intriguingly, we found that the effect of chrysin was also reduced by FGFR1 blockade. Moreover, extended treatment of chrysin enhanced levels of brain-derived neurotrophic factor, as well as FGF1 and FGF8. Finally, chrysin was found to promote neurogenesis in human cerebral organoids by increasing the organoid expansion and folding, which was also mediated by TrkB and FGFR1 signalling. To conclude, our study indicates that activating both TrkB and FGFR1 signalling could be a promising avenue for therapeutic interventions in neurological diseases, and chrysin appears to be a potential candidate for the development of such treatments.

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at least in part through the regulation of retinoic acid receptor α (RXRα), a modulator of Wnt/β-catenin signalling. Repression of miR-27a-3p increases the expression of RXRα and concomitantly, decreases the expression of active β-catenin and cyclin D1. In contrast, overexpression of miR-27a-3p mimic decreases the expression of RXRα and increases the expression of active β-catenin and cyclin D1. Moreover, overexpression of the miR-27a-3p mimic results in impaired enterocyte differentiation and increases intestinal epithelial cell proliferation. These alterations were attenuated or blocked by Wnt inhibition. Our study demonstrates an miR-27a-3p/RXRα/Wnt/β-catenin pathway that is important for the maintenance of enterocyte homeostasis in the small intestine.

As major somatic cells in the testis, Sertoli cell development is precisely regulated by numerous factors, and aberrant development of these cells is associated with male reproductive diseases. JNK signalling is evolutionarily conserved and involved in multiple critical biological processes. Here, we found that the double knockout of Jnk1 and Jnk2 resulted in aberrant localisation of Sertoli cells at early developmental stages, with most Sertoli cells being lost at later stages. Further studies revealed that the inactivation of JNK signalling caused polarity loss in Sertoli cells. In vitro-cultured Jnk1/2-DKO Sertoli cells exhibited a senescence-associated phenotype. Mechanistic studies demonstrate that JNK signalling is likely involved in establishing Sertoli cell polarity by regulating the expression of TGF-β2, mediated by c-Jun. The senescence of Sertoli cells in JNKs-deficient mice is caused by aberrant proteolysis of P27^KIP1, mediated by c-Myc. This study demonstrates the role of JNK signalling in Sertoli cell development and functional maintenance, which may also represent an aetiology of male infertility in humans.

Zhou X, Yu R, Long Y, et al. BMAL1 deficiency promotes skeletal mandibular hypoplasia via OPG downregulation. Cell Prolif. 2018;51:e12470. doi:10.1111/cpr.12470.

The Western blot bands of OPG in Figure 4A of BMAL1-overexpressed BMSCs and BMAL1 in Figure 4B of BMAL1-overexpressed MC3T3-E1 cell line were incorrectly copied.

Corrected Figure 4 is provided below. The correction does not alter any findings and conclusions reported in this article.

We apologize for this error.

C. Ji, J. Gao, and Y. Huang, “ Legionella Pneumophila Infection Reduces the Mitochondrial Membrane Potential Through Lpg2444-Inhibited Mitocytosis,” Cell Proliferation (Early View): https://doi.org/10.1111/cpr.13660.

The above article, published online on 19 May 2024 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Deputy Editor, Yunfeng Lin; and John Wiley & Sons Ltd. Following additional research, the authors observed results that called into question their original findings. The retraction has been agreed due to a lack of sufficient data to support the article's conclusion.