bims-migras 2025-12-07 papers

Issue of 2025–12–07
four papers selected by
Cliff Dominy

Physiology (Bethesda). 2025 Dec 05.

The Role of Migrasomes in Health and Disease.

Migrasomes are specialized organelle that form during cell migration and play a critical role in intercellular communication and disease progression. First discovered in 2012 and reported in 2015, these organelles are characterized by their unique biogenesis on retraction fibers and their role in spatiotemporal signaling, distribution of bioactive molecules, and maintenance of cellular homeostasis. This review provides a comprehensive overview of migrasome biology, exploring their discovery, mechanisms of formation, physiological functions, and pathological implications. We examine their dual roles in both health and disease, highlighting their potential as diagnostic biomarkers and therapeutic targets. Additionally, we discuss the challenges and future directions in migrasome research, emphasizing the importance of foundational discoveries and advanced methodologies to fully realize their clinical potential.

Keywords: Intercellular communication; Migrasome

DOI: https://doi.org/10.1152/physiol.00025.2025

Adv Sci (Weinh). 2025 Nov 30. e11683

ITM2B Truncation Promotes Migrasome Formation to Accelerate Renal Cell Carcinoma Growth.

Qi-Tao Chen, Qiao-Ling Huang, Ming-Zhi Han, Xue-Hui Hong, De-Yi Feng, Lu-Ming Yao, Wen-Bin Hong, Yue Chen, Ya-Ying Huang, Hang-Zi Chen, Qiao Wu.

Integral membrane protein 2B (ITM2B), a transmembrane protein, frequently undergoes cleavage. The physiological functions of ITM2B are primarily studied in the context of neurological disorders, but their roles in cancers are largely overlooked. Here, it is demonstrated that in renal cell carcinoma (RCC) cells, N-terminal truncation of ITM2B facilitates migrasome swelling through the recruitment of TSPAN4 and promotes migrasome formation. Moreover, ITM2B truncation acts as a carrier, sorting active caspase-7 into migrasomes for migracytosis. The active caspase-7-enriched migrasomes are then taken up by macrophages, leading to caspase-7-induced IL-6 secretion from macrophages, which eventually aggravates RCC growth through a feedback mechanism. Physiologically, hyperuricemia enhances ITM2B cleavage to aggravate RCC growth. Clinically, RCC tissues tend to produce ITM2B truncations compared with corresponding para-carcinoma tissues. Moreover, compared with the urine from normal volunteers, that from RCC patients contains higher levels of ITM2B truncation-enriched migrasomes. This study not only highlights novel functions of ITM2B truncation in migrasome formation and active caspase-7 migracytosis but also elucidates the role of hyperuricemia in RCC progression via regulation of the ITM2B truncation-migrasome axis.

Keywords: caspase‐7; integral membrane protein 2B (ITM2B); migrasomes; renal cell carcinoma (RCC); tetraspanin 4 (TSPAN4)

DOI: https://doi.org/10.1002/advs.202511683

Adv Sci (Weinh). 2025 Dec 03. e20608

Migrasomes in Ischemic Stroke: Molecular Landscape and Pathophysiological Impact.

Huifen Zhou, Yingying Zhang, Peng Zhou, Haofang Wan, Lingling Li, Bin Xu, Yuping Wan, Yingming Song, Yi Kang, Hongbo Zhang, Min Shi, Qun Hou, Jiehong Yang, Chen Ding, Wei Fu, Buchang Zhao, Haitong Wan.

Ischemic stroke (IS) initiates complex systemic responses that extend beyond focal brain injury. To capture these multifaceted changes, proteomics, untargeted metabolomics, and lipidomics are integrated from IS patients spanning a range of clinical severities. This multi-omics approach reveals distinct molecular subtypes characterized by immune activation, oxidative stress, and metabolic dysregulation. Notably, elevated levels of migrasomes are identified in patient plasma and mouse brain tissue. Proteomic profiling of these migrasomes shows enrichment in complement, coagulation, and cholesterol-associated pathways. Functional assays further demonstrate that migrasomes derived from peripheral immune cells exacerbate ischemic injury and intensify post-stroke inflammation. Together, these findings position migrasomes as critical drivers of IS pathophysiology and highlight them as promising targets for therapeutic intervention.

Keywords: ischemic stroke; migrasomes; proteomics; untargeted lipidomics; untargeted metabolomics

DOI: https://doi.org/10.1002/advs.202520608

Sci Rep. 2025 Dec 02.

Jinlin Cai, Jiaxi Fei, Jing Wang, Qinbo Wang, Junrong Chen.

Migrasome has recently been reported to regulate cell-cell communication in tumor progression. But the function of migrasome in CRC, especially its prognostic potential and association with long non-coding RNAs and tumor microenvironment has yet to be fully explored. Migrasome-related lncRNAs were identified based on transcriptome data from 650 CRC patients in the TCGA COREAD cohort. A prognostic signature was developed via the least absolute shrinkage and selection operator algorithm and Cox regression. The multimodal predicting model for prognosis of CRC patients was constructed and validated through Kaplan-Meier survival, ROC curve analysis, and nomogram construction. Patients were divided into high- and low-risk groups according to their prognostic signature and functional enrichment, immune cell infiltration, immunotherapy efficacy, and drug sensitivity analyses were performed to characterize their variation. Ten migrasome-related lncRNAs were identified and used to construct a prognostic risk score that effectively stratified patients into high- and low-risk groups, demonstrating significant differences in overall survival (P < 0.001) and survival-related ROC curve analysis. A nomogram based on the multimodal predicting model was constructed with robust calibration curves. The transcriptional variation between high-risk and low-risk patients were mainly associated with signaling receptor activator activity, receptor ligand activity and cytokine-cytokine receptor interaction. High-risk patients exhibited reduced immune cell infiltration and higher potential for immune escape. In addition, drug sensitivity screening revealed that high-risk patients were more likely to resist current targeted drugs including PLX-4720 and JAK-8517 than low-risk patients. This study identifies a novel migrasome-related lncRNA signature as a reliable prognostic tool for CRC, highlighting its potential in patient stratification and personalized therapy.

Keywords: Colorectal cancer; LncRNA; Migrasome; Prognosis

DOI: https://doi.org/10.1038/s41598-025-29304-8