{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:11:42Z","timestamp":1791223902625,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T00:00:00Z","timestamp":1406592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2014,7,29]],"date-time":"2014-07-29T00:00:00Z","timestamp":1406592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Glioblastoma (GBM) remains the most aggressive and lethal brain tumor due to its molecular heterogeneity and high motility and invasion capabilities of its cells, resulting in high resistance to current standard treatments (surgery, followed by ionizing radiation combined with Temozolomide chemotherapy administration). Locus amplification, gene overexpression, and genetic mutations of epidermal growth factor receptor (\n                      <jats:italic>EGFR<\/jats:italic>\n                      ) are hallmarks of GBM that can ectopically activate downstream signaling oncogenic cascades such as PI3K\/Akt\/mTOR pathway. Importantly, alteration of this pathway, involved also in the regulation of autophagy process, can improve radioresistance in GBM cells, thus promoting the aggressive phenotype of this tumor. In this work, the endogenous EGFR expression profile and autophagy were modulated to increase radiosensitivity behavior of human T98G and U373MG GBM cells. Our results primarily indicated that\n                      <jats:italic>EGFR<\/jats:italic>\n                      interfering induced radiosensitivity according to a decrease of the clonogenic capability of the investigated cells, and an effective reduction of the in vitro migratory features. Moreover,\n                      <jats:italic>EGFR<\/jats:italic>\n                      interfering resulted in an increase of Temozolomide (TMZ) cytotoxicity in T98G TMZ\u2010resistant cells. In order to elucidate the involvement of the autophagy process as pro\u2010death or pro\u2010survival role in cells subjected to\n                      <jats:italic>EGFR<\/jats:italic>\n                      interfering, the key autophagic gene\n                      <jats:italic>ATG7<\/jats:italic>\n                      was silenced, thereby producing a transient block of the autophagy process. This autophagy inhibition rescued clonogenic capability of irradiated and\n                      <jats:italic>EGFR<\/jats:italic>\n                      \u2010silenced T98G cells, suggesting a pro\u2010death autophagy contribution. To further confirm the functional interplay between EGFR and autophagy pathways, Rapamycin\u2010mediated autophagy induction during\n                      <jats:italic>EGFR<\/jats:italic>\n                      modulation promoted further impairment of irradiated cells, in terms of clonogenic and migration capabilities. Taken together, these results might suggest a novel combined EGFR\u2010autophagy modulation strategy, to overcome intrinsic GBM radioresistance, thus improving the efficacy of standard treatments. J. Cell. Physiol. 229: 1863\u20131873, 2014. \u00a9 2014 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.24640","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T07:14:26Z","timestamp":1396336466000},"page":"1863-1873","source":"Crossref","is-referenced-by-count":46,"title":["Combined EGFR and Autophagy Modulation Impairs Cell Migration and Enhances Radiosensitivity in Human Glioblastoma Cells"],"prefix":"10.1002","volume":"229","author":[{"given":"Silvia","family":"Palumbo","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience (Radiotherapy Unit) University Hospital of Siena Siena 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