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Cancer\u2010associated fibroblasts (CAFs) are key in the ESCC microenvironment, yet their role in post\u2010radiation recurrence remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>KYSE150 ESCC cells were co\u2010implanted with non\u2010irradiated (0\u00a0Gy) or irradiated (8\u00a0Gy) CAFs in nude mice. CAF\u2010derived extracellular vesicles (EVs) were isolated via differential centrifugation and analysed by electron microscopy and immunoblotting. Transwell assays evaluated EVs' effects on ESCC cell migration and invasion in vitro. RNA sequencing identified differentially expressed microRNAs, and functional experiments verified the role of miR\u2010193a\u20103p. Plasma samples from 32 ESCC patients and tissue samples from 76 ESCC patients were analysed for miR\u2010193a\u20103p expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Irradiated CAFs promoted the lung metastasis of ESCC cells in vivo, and their EVs enhanced ESCC cell invasion, migration and metastasis. Elevated miR\u2010193a\u20103p levels in EVs from irradiated CAFs increased miR\u2010193a\u20103p expression in ESCC cells. This effect was effectively attenuated by RNase and Triton X\u2010100 (degrading microRNAs encapsulated in EVs), or GW4869 (inhibiting EVs biogenesis and secretion)\u2014indicating that miR\u2010193a\u20103p functions in an EV\u2010dependent manner. Knockdown of miR\u2010193a\u20103p diminished the invasion, migration and epithelial\u2013mesenchymal transition (EMT)\u2010promoting activities of CAF\u2010derived EVs. Luciferase assays confirmed PTEN as a target of miR\u2010193a\u20103p; miR\u2010193a\u20103p overexpression decreased PTEN and increased p\u2010Akt expression. In vivo, coinjection of miR\u2010193a\u20103p\u2010knockdown CAFs with KYSE150 ESCC cells resulted in smaller tumours, fewer lung metastases, increased PTEN and E\u2010cadherin, and decreased p\u2010Akt and Snail expression. Clinically, radiation increased plasma exosomal miR\u2010193a\u20103p levels, and high miR\u2010193a\u20103p expression was correlated with shorter survival, identifying miR\u2010193a\u20103p as an independent predictor of poor prognosis in ESCC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EVs from irradiated CAFs promote ESCC metastasis via the miR\u2010193a\u20103p\u2010mediated PTEN\/Akt signalling pathway. Targeting this EVs\u2010mediated interaction represents a promising strategy for improving ESCC radiotherapy outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>The poor prognosis of oesophageal squamous cell carcinoma (ESCC) is largely driven by recurrence and metastasis following radiation therapy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Irradiated cancer\u2010associated fibroblasts (CAFs) drive ESCC recurrence and metastasis through extracellular vesicles (EVs), highlighting their critical role in the post\u2010radiation tumor microenvironment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CAF\u2010derived EVs deliver miR\u2010193a\u20103p to ESCC cells, suppressing PTEN and activating Akt signaling, thereby enhancing invasion, migration, epithelialmesenchymal transition (EMT), and metastatic potential.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High plasma exosomal miR\u2010193a\u20103p levels predict poor prognosis in ESCC patients and may guide therapeutic strategies after radiotherapy.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70483","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T06:45:37Z","timestamp":1758869137000},"source":"Crossref","is-referenced-by-count":7,"title":["Radiation\u2010induced extracellular vesicles from cancer\u2010associated fibroblasts drive oesophageal squamous 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