bims-migras 2025-09-14 papers

Issue of 2025–09–14
three papers selected by
Cliff Dominy

Cell Physiol Biochem. 2025 Sep 06. 59(5): 589-608

Migrasomes in Health and Disease: Insights into Mechanisms, Pathogenesis, and Therapeutic Opportunities.

Lauryn Akeme, Pollyanna Sibanda, Aisling Fitzgerald, Agnieszka Bossowska, Klaudia Bonowicz, Dominika Jerka, Maciej Gagat.

Migrasomes are newly discovered, migration-dependent organelles that mediate the release of cellular contents into the extracellular environment through a process known as migracytosis. Since their identification in 2014, growing evidence has highlighted their critical roles in intercellular communication, organ development, mitochondrial quality control, and disease pathogenesis. Migrasome biogenesis is a complex, multi-step process tightly regulated by lipid composition, tetraspanin-enriched microdomains, and molecular pathways involving sphingomyelin synthase 2, Rab35, and integrins. Unlike exosomes, migrasomes possess distinct structural and functional characteristics, which position them as novel organelles rather than classic extracellular vesicles. Recent studies have revealed their involvement in diverse pathological contexts, including kidney disease, cancer progression, proliferative vitreoretinopathy, viral infections, and myocardial infarction. Notably, migrasomes hold promise as diagnostic biomarkers, especially in early podocyte injury, and as therapeutic targets in oncology and regenerative medicine. This review summarizes the current understanding of migrasome biology, and their implications in health and disease, and explores emerging perspectives on harnessing migrasomes for diagnostic and therapeutic applications.

Keywords: Migrasomes ; Migracytosis ; Intercellular communication ; Tetraspanins

DOI: https://doi.org/10.33594/000000810

Nat Aging. 2025 Sep 10.

Senescent-like border-associated macrophages regulate cognitive aging via migrasome-mediated induction of paracrine senescence in microglia.

Mengyan Hu, Xinmei Kang, Zhiruo Liu, Shisi Wang, Sanxin Liu, Chunyi Li, Danli Lu, Qin Qin, Yuxin Liu, Haotong Yi, Liling Yuan, Quentin Liu, Zhengqi Lu, Wei Cai.

Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging, possibly due to prolonged exposure to amyloid beta. Senescent-like BAMs show elevated production of migrasomes, which convey senescence-associated signals including the apoptosis inhibitor of macrophage to neighboring cells. We show that microglia are prominent recipients of senescent-like BAM-derived migrasomes, and that through activation of CD16 in recipient cells, the apoptosis inhibitor of macrophage inhibits apoptosis and promotes senescence induction. Blocking migrasome induction in senescent-like BAMs through treatment with Tspan4-targeting siRNA-encapsulated liposomes ameliorates cognitive deficits in aged mice. Our findings suggest that migrasomes are potent vehicles of senescence-regulatory signals and represent a promising target for senomorphic therapy.

DOI: https://doi.org/10.1038/s43587-025-00956-5

Ann Med. 2025 Dec;57(1): 2558121

Development and validation of a novel risk stratification signature derived from migrasome and tumor microenvironment-related genes for molecular subtyping and improving clinical outcomes in head and neck squamous cell carcinoma.

Huifang Chai, Chuchu Zhou, Zixin Xue, Min Zhang, Ling Qiao, Jianjun Wang, Feng Lu.

BACKGROUND: The tumor microenvironment (TME) and migrasomes released by tumor cells significantly influence carcinogenesis and immune evasion. However, our understanding of the prognostic and therapeutic implications of migrasome and tumor microenvironment-related genes (mtmRGs) in head and neck squamous cell carcinoma (HNSCC) remains limited.
METHODS: We explored the relationship between mtmRGs and HNSCC prognosis by utilizing The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Subsequently, we developed an innovative prognostic signature, and assessed its prognostic significance using the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and Cox regression analyses. To explore the underlying mechanisms, we conducted gene set variation analysis (GSVA), gene set enrichment analysis (GESA), and immune infiltration analysis. A nomogram was developed to estimate the overall survival (OS) rates for HNSCC patients. Lastly, we chose P4HA1, which was part of the signature, for additional experimental validation in vitro and in vivo.
RESULTS: The mtmRGs signature effectively classifies HNSCC patients into two distinct risk subgroups, with the high-risk cohort demonstrating significantly poorer OS. The risk score serves as an independent prognostic factor for HNSCC patients; those with lower risk scores are more likely to exhibit favorable responses to immunotherapy, particularly with CTLA4 inhibitors. Furthermore, a lower risk score is significantly correlated with the sensitivity of HNSCC patients to cyclophosphamide, gemcitabine, and axitinib.
CONCLUSION: This study presents an innovative gene signature associated with mtmRGs, which may be utilized both for predicting survival and directing personalized chemotherapy and immunotherapy regiments for patients with HNSCC.

Keywords: Migrasome; head and neck squamous cell carcinoma; prognostic signature; tumor microenvironment

DOI: https://doi.org/10.1080/07853890.2025.2558121