{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:37:32Z","timestamp":1777495052312,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER, COMPETE 2020, POCI, Portugal 2020, FCT","award":["POCI-01-0145-FEDER-007274"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274"]}]},{"name":"NORTE2020, PORTUGAL2020, ERDF","award":["NORTE-01-0145-FEDER-000003"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000003"]}]},{"name":"NORTE2020, PORTUGAL2020, ERDF","award":["NORTE-01-0145-FEDER-000029"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000029"]}]},{"name":"ERDF, POCI, FCT","award":["POCI-01-0145-FEDER-016390"],"award-info":[{"award-number":["POCI-01-0145-FEDER-016390"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CTM-NAN\/120958\/2010"],"award-info":[{"award-number":["PTDC\/CTM-NAN\/120958\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/113031\/2015"],"award-info":[{"award-number":["SFRH\/BD\/113031\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"POPH, QREN, ESF, MCTES","award":["IF\/00615\/2013"],"award-info":[{"award-number":["IF\/00615\/2013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>De novo expressed CD44 isoforms containing exon-v6 are frequently associated with gastric cancer (GC) aggressiveness, and may predict chemotherapy response in vitro. Whether exon-v6 itself is responsible for conferring these properties to CD44v6-containing isoforms remains to be elucidated. CRISPR\/Cas9 and Phosphorodiamidate Morpholino oligomers (PMOs) were used to induce specific exon-v6 skipping, maintaining the CD44 reading frame, in two GC cell lines endogenously expressing CD44v6. Cisplatin and 5-fluorouracil treatment response, and self-renewal ability was compared between CRISPR\/Cas9-edited, CD44v6 knockdown and mock cells. We obtained homozygous genome-edited cell lines with exon-v6 deletion. Edited cells transcribed CD44v isoforms presenting in frame v5\u2013v7 splicing, mimicking exon-v6 skipping. Results showed that removing specifically exon-v6 sensitizes cells to cisplatin and impairs cells\u2019 self-renewal ability, similarly to CD44v6 knockdown. In parallel, we also tested a clinically feasible approach for transient exon-v6 skipping with a PMO-based strategy. We demonstrate that exon-v6 specific removal from CD44v isoforms increases cell sensitivity to cisplatin and impairs GC cells self-renewal. We trust that a PMO approach designed towards CD44v6 overexpressing GC cells may be a suitable approach to sensitize tumor cells for conventional therapy.<\/jats:p>","DOI":"10.3390\/cancers12092378","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"2378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Skipping Exon-v6 from CD44v6-Containing Isoforms Influences Chemotherapy Response and Self-Renewal Capacity of Gastric Cancer Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5705-2958","authenticated-orcid":false,"given":"Silvana","family":"Lobo","sequence":"first","affiliation":[{"name":"i3s\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-0764","authenticated-orcid":false,"given":"Carla","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3s\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"Doctoral Programme in Biomedicine, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-2264","authenticated-orcid":false,"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3s\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"FMUP\u2013Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-7394","authenticated-orcid":false,"given":"Gabriela M.","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3s\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"FMUP\u2013Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/annonc\/mdw350","article-title":"Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Smyth","year":"2016","journal-title":"Ann. 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