Stathmin 1 regulates mitophagy and cellular function in hematopoietic stem cellsChiquetto, Schuetz, Dong
et albioRxiv (2025)
Abstract: Stathmin 1 is a cytoplasmic phosphoprotein that regulates microtubule dynamics via promotion of microtubule catastrophe and sequestration of free tubulin heterodimers. Stathmin 1 is highly expressed in hematopoietic stem cells (HSCs), and overexpressed in leukemic cells, however its role in HSCs is not known. Herein, we found that loss of Stathmin 1 is associated with altered microtubule architecture in HSCs, and markedly impaired HSC function. Transcriptomic studies suggested alterations in oxidative phosphorylation in Stmn1 -/- HSCs, and further mechanistic studies revealed defective mitochondrial structure and function in the absence of Stathmin 1 with increased ROS production. Microtubules associate with mitochondria and lysosomes to facilitate autophagosome formation and mitophagy, and indeed we found that this critical mitochondrial quality control process is impaired in Stathmin 1-deficient HSCs. Finally, stimulation of autophagy improved the colony forming ability of Stmn1 -/- hematopoietic stem and progenitor cells. Together, our data identify Stathmin 1 as a novel regulator of mitophagy and mitochondrial health in HSCs.The microtubule regulating protein Stathmin 1 is highly expressed in HSPCs and promotes normal microtubule architecture.Loss of Stathmin 1 in HSPCs leads to impaired autophagy with abnormal mitochondrial morphology, decreased respiratory capacity, and impaired cellular function.
C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7Wang, Smeyers, Eggan
et alActa Neuropathol Commun (2025) 13 (1), 67
Abstract: A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and combined ALS/FTD. The repeat is transcribed in the sense and the antisense directions to produce several dipeptide repeat proteins (DPRs) that have toxic gain-of-function effects; however, the mechanisms by which DPRs lead to neural dysfunction remain unresolved. Here, we observed that poly-proline-arginine (poly-PR) was sufficient to inhibit axonal regeneration of human induced pluripotent stem cell (iPSC)-derived neurons. Global phospho-proteomics revealed that poly-PR selectively perturbs nuclear RNA binding proteins (RBPs). In neurons, we found that depletion of one of these RBPs, SRSF7 (serine/arginine-rich splicing factor 7), resulted in decreased abundance of STMN2 (stathmin-2), though not TDP-43. STMN2 supports axon maintenance and repair and has been recently implicated in the pathogenesis of ALS/FTD. We observed that depletion of SRSF7 impaired axonal regeneration, a phenotype that could be rescued by exogenous STMN2. We propose that antisense repeat-encoded poly-PR perturbs RBPs, particularly SRSF7, resulting in reduced STMN2 and axonal repair defects in neurons. Hence, we provide a potential link between DPRs gain-of-function effects and STMN2 loss-of-function phenotypes in neurodegeneration.© 2025. The Author(s).
Prognostic role of STMN1 expression and neoadjuvant therapy efficacy in breast cancerQian, Cairong, Yongdong
et alBMC Cancer (2025) 25 (1), 453
Abstract: breast cancer is common and highly malignant, currently, STMN1 was found to be associated with several human malignancies. The purpose of this study is to investigate STMN1 expression in breast cancer and explore its role in disease progression and its interaction with neoadjuvant therapy efficacy.we analyzed the tissue STMN1 mRNA expression in BC tissue samples from 105 patients received with neoadjuvant therapy using qPCR between 2019 and 2022.Statistical analysis showed that a high expression of STMN1 before neoadjuvant chemotherapy (NACT) was a trend positively related to non-pCR in the ITT (Intention to Treat) population, while in patients with paclitaxel or docetaxel regimens, before-NACT STMN1 expression was obviously higher in non-pCR (failure to achieve pathologically complete response) patients. Additionally, compared to pCR, high expression of STMN1 after NACT was obviously related to non-pCR. Interestingly, Kaplan-Meier analysis demonstrated that patients with mid-high STMN1 expression before and post-NACT had a poorer PFS to compared to those with low expression.STMN1 is the potential biomarker of NACT and prognosis for breast cancer.© 2025. The Author(s).
Eribulin exerts multitarget antineoplastic activity in glioma cellsAlcântara, do Nascimento, de Miranda
et alPharmacol Rep (2025)
Abstract: Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates the cellular and molecular effects of eribulin in glioma models, focusing on its impact on cell cycle progression, apoptosis, mitochondrial function, and migration.Glioma cell lines were treated with eribulin. Cell viability was measured by MTT assay, and the cell cycle was analyzed by flow cytometry. Apoptosis was assessed through morphological changes, PARP1 cleavage, and γH2AX expression. Mitochondrial integrity and reactive oxygen species levels were evaluated by flow cytometry. Cell migration was assessed using a spheroid-based assay, and protein expression changes were analyzed by Western blotting.Eribulin reduced cell viability, with HOG cells exhibiting the highest sensitivity. Cell cycle analysis showed G2/M phase arrest and morphological examination revealed polyploidy and apoptotic features. Mitochondrial dysfunction was observed, with decreased mitochondrial membrane potential and increased reactive oxygen species, particularly in HOG and T98G cells. Molecular analysis indicated activation of apoptotic pathways (PARP1 cleavage and γH2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.Eribulin demonstrates potent anti-glioma effects through apoptosis, mitochondrial dysfunction, and cell cycle disruption. These findings support its potential as a therapeutic option for glioblastoma treatment, warranting further investigation into its mechanisms and clinical applicability.© 2025. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.
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