AI Article Synopsis
- - Triple-negative breast cancer (TNBC) is a highly lethal subtype of breast cancer, and the study focuses on how extracellular vesicles (EVs) derived from TNBC tumors promote tumor growth by influencing macrophage polarization towards an M2 phenotype.
- - The research discovered that the long non-coding RNA (lncRNA) MALAT1 is packaged in TNBC-derived EVs and, upon being transferred to macrophages, enhances M2 polarization, which is linked to worse patient prognosis.
- - The findings suggest that MALAT1 activates the Hippo/YAP signaling pathway through the upregulation of POSTN, thereby facilitating both the onset and spread of TNBC, indicating potential therapeutic targets for intervention.
Article Abstract
Objectives: Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis.
Methods: BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining.
Results: MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC in vitro and in vivo.
Conclusions: TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis in vivo.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402314 | PMC |
| http://dx.doi.org/10.1016/j.tranon.2024.102076 | DOI Listing |
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