bims-migras 2026-06-21 papers

Issue of 2026–06–21
two papers selected by
Cliff Dominy

Cell Death Dis. 2026 Jun 15.

CD147-positive migrasome macropinocytosis promotes HCC sorafenib resistance via inducing vasculogenic mimicry triggered by PI3K/AKT/TWIST1 signaling.

Luomeng Qian, Ping Chen, Bo Wang, Qing Zhang, Yuan Guo, Jie Cui, Ran Ding, Hongkai Zhang, Sihe Zhang.

Sorafenib is a widely used targeting drug for hepatocellular carcinoma (HCC) patients; however, sorafenib resistance poses a significant clinical challenge. Hypoxia and extracellular vesicles (EVs) induce vasculogenic mimicry (VM) which is linked to sorafenib resistance in HCC. Migrasomes (Migs), the newly discovered large EVs, foster HCC malignant phenotypes by facilitating the intercellular transfer of functional molecules. Despite these advancements, the precise mechanism by which Migs cause sorafenib resistance is still unknown. In this study, we found that hypoxia upregulates the Migs release and CD147 expression on Migs surface, which is related to sorafenib resistance in HCC. Further investigations revealed that hypoxia-induced migrasomes (hypo-Migs) induce VM formation, thereby promoting sorafenib resistance in HCC. Notably, hypo-Migs are internalized into HCC cells through macropinocytosis, which depends on the expression of lysophosphatidic acid receptor 6 (LPAR6). Mechanistically, CD147-positive (CD147+) hypo-Migs activate the PI3K/AKT/TWIST1 signaling pathway, subsequently inducing VM formation and promoting sorafenib resistance. Importantly, dual blockade of CD147+-hypo-Migs macropinocytosis and VM formation enhances the sorafenib-killing efficacy to HCC. Conclusively, our findings uncover a novel sorafenib resistance mechanism induced by CD147+-hypo-Migs, and highlight dual-targeting of macropinocytosis and VM as a promising strategy to overcome the sorafenib resistance in HCC.

DOI: https://doi.org/10.1038/s41419-026-08972-y

Nat Rev Mol Cell Biol. 2026 Jun 19.

Regulation and function of specialized membrane protrusions in intercellular communication.

Shiyu Liu, Christina A Daly, Stacey K Ogden, Chiara Zurzolo.

Cells use specialized membrane extensions that enable the exchange of signals, organelles and other cargo to support long-range communication within complex tissues. Among these, tunnelling nanotubes, cytonemes and migrasomes have emerged as key contributors to development, immune responses and disease. Growing evidence has revealed that these structures are more prevalent and functionally diverse than previously appreciated, prompting a re-evaluation of how cells coordinate behaviour across space. In this Review, we discuss recent advances in understanding the formation, regulation and specificity of these dynamic connections, with an emphasis on tunnelling nanotubes and cytonemes, and highlight common principles underlying their architecture and cargo transfer. We further explore how their dysregulation contributes to pathology, underscoring the need to integrate these structures into current models of tissue organization.

DOI: https://doi.org/10.1038/s41580-026-00982-0