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However, most patients eventually experience tumour recurrence, treatment failure and metastatic dissemination with fatal consequences. To elucidate the molecular mechanisms of resistance to radio\u2010 and chemotherapy, we exposed human cancer cell lines (HeLa, MCF\u20107 and\n                    <jats:styled-content style=\"fixed-case\">DU<\/jats:styled-content>\n                    145) to clinically relevant doses of 5\u2010azacytidine or ionizing radiation and compared the transcript profiles of all surviving cell subpopulations, including low\u2010adherent stem\u2010like cells. Stress\u2010mobilized low\u2010adherent cell fractions differed from other survivors in terms of deregulation of hundreds of genes, including those involved in interferon response. Exposure of cancer cells to interferon\u2010gamma but not interferon\u2010beta resulted in the development of a heterogeneous, low\u2010adherent fraction comprising not only apoptotic\/necrotic cells but also live cells exhibiting active Notch signalling and expressing stem\u2010cell markers. Chemical inhibition of mitogen\u2010activated protein kinase\/ERK kinase (\n                    <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\n                    ) or si\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \u2010mediated knockdown of extracellular signal\u2010regulated kinase 1\/2 (Erk1\/2) and interferon responsible factor 1 (\n                    <jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>\n                    1) prevented mobilization of the surviving low\u2010adherent population, indicating that interferon\u2010gamma\u2010mediated loss of adhesion and anoikis resistance required an active Erk pathway interlinked with interferon signalling by transcription factor\n                    <jats:styled-content style=\"fixed-case\">IRF<\/jats:styled-content>\n                    1. Notably, a skin\u2010specific protein suprabasin (\n                    <jats:styled-content style=\"fixed-case\">SBSN<\/jats:styled-content>\n                    ), a recently identified oncoprotein, was among the top scoring genes upregulated in surviving low\u2010adherent cancer cells induced by 5\u2010azacytidine or irradiation.\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SBSN<\/jats:styled-content>\n                    <\/jats:italic>\n                    expression required the activity of the\n                    <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\n                    \/Erk pathway, and si\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \u2010mediated knockdown of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">SBSN<\/jats:styled-content>\n                    <\/jats:italic>\n                    suppressed the low\u2010adherent fraction in irradiated, interferon\u2010gamma\u2010 and 5\u2010azacytidine\u2010treated cells, respectively, implicating\n                    <jats:italic>SBSN<\/jats:italic>\n                    in genotoxic stress\u2010induced phenotypic plasticity and stress resistance. Importantly,\n                    <jats:italic>SBSN<\/jats:italic>\n                    expression was observed in human clinical specimens of colon and ovarian carcinomas, as well as in circulating tumour cells and metastases of the 4T1 mouse model. The association of\n                    <jats:italic>SBSN<\/jats:italic>\n                    expression with progressive stages of cancer development indicates its role in cancer evolution and therapy resistance.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.12480","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T02:45:34Z","timestamp":1553741134000},"page":"1467-1489","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Interferon\u2010regulated suprabasin is essential for stress\u2010induced stem\u2010like cell conversion and therapy resistance of human malignancies"],"prefix":"10.1002","volume":"13","author":[{"given":"Sona","family":"Hubackova","sequence":"first","affiliation":[{"name":"Laboratory of Genome Integrity Institute of Molecular Genetics of the ASCR, v. v. i. 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