{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:02:47Z","timestamp":1763535767253,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T00:00:00Z","timestamp":1601683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KFO325,  GRK2573, PO1408\/13-1"],"award-info":[{"award-number":["KFO325,  GRK2573, PO1408\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Drugs targeting epigenetic mechanisms such as histone deacetylase inhibitors (HDACi) suppress tumor growth. HDACi also induce the expression of ligands for the cytotoxicity receptor NKG2D rendering tumors more susceptible to natural killer (NK) cell-dependent killing. The major acetylases responsible for the expression of NKG2D ligands (NKG2D-L) are CBP and p300. The role of the oncogene and transcriptional repressor SKI, an essential part of an HDAC-recruiting co-repressor complex, which competes with CBP\/p300 for binding to SMAD3 in TGF\u03b2 signaling, is unknown. Here we show that the siRNA-mediated downregulation of SKI in the pancreatic cancer cell lines Panc-1 and Patu8988t leads to an increased target cell killing by primary NK cells. However, the higher cytotoxicity of NK cells did not correlate with the induction of NKG2D-L. Of note, the expression of NKG2D-L and consequently NK cell-dependent killing could be induced upon LBH589 (LBH, panobinostat) or valproic acid (VPA) treatment irrespective of the SKI expression level but was significantly higher in pancreatic cancer cells upon genetic ablation of SKI. These data suggest that SKI represses the inducible expression of NKG2D-L. The combination of HDACi with NK cell-based immunotherapy is an attractive treatment option for pancreatic tumors, specifically for patients with high SKI protein levels.<\/jats:p>","DOI":"10.3390\/cancers12102857","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T08:35:57Z","timestamp":1601886957000},"page":"2857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Oncoprotein SKI Acts as A Suppressor of NK Cell-Mediated Immunosurveillance in PDAC"],"prefix":"10.3390","volume":"12","author":[{"given":"Viviane","family":"Ponath","sequence":"first","affiliation":[{"name":"Institute for Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University of Marburg, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Frech","sequence":"additional","affiliation":[{"name":"Clinic for Hematology, Oncology, Immunology and Center for Tumor Biology and Immunology, Philipps University of Marburg, Baldingerstrasse, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathis","family":"Bittermann","sequence":"additional","affiliation":[{"name":"Institute for Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University of Marburg, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Al Khayer","sequence":"additional","affiliation":[{"name":"Institute for Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University of Marburg, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7606-8760","authenticated-orcid":false,"given":"Andreas","family":"Neubauer","sequence":"additional","affiliation":[{"name":"Clinic for Hematology, Oncology, Immunology and Center for Tumor Biology and Immunology, Philipps University of Marburg, Baldingerstrasse, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-9557","authenticated-orcid":false,"given":"Cornelia","family":"Brendel","sequence":"additional","affiliation":[{"name":"Clinic for Hematology, Oncology, Immunology and Center for Tumor Biology and Immunology, Philipps University of Marburg, Baldingerstrasse, 35037 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Pogge von Strandmann","sequence":"additional","affiliation":[{"name":"Institute for Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Philipps University of Marburg, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1101\/gad.275776.115","article-title":"Genetics and biology of pancreatic ductal adenocarcinoma","volume":"30","author":"Ying","year":"2016","journal-title":"Genes Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer Statistics","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J. 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