{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:39:55Z","timestamp":1792067995024,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NCI","award":["R01 CA208108"],"award-info":[{"award-number":["R01 CA208108"]}]},{"name":"NIH\/NCI","award":["P01 CA217798"],"award-info":[{"award-number":["P01 CA217798"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated levels of Mucin-16 (MUC16) in conjunction with a high expression of truncated O-glycans is implicated in playing crucial roles in the malignancy of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms by which such aberrant glycoforms present on MUC16 itself promote an increased disease burden in PDAC are yet to be elucidated. This study demonstrates that the CRISPR\/Cas9-mediated genetic deletion of MUC16 in PDAC cells decreases tumor cell migration. We found that MUC16 enhances tumor malignancy by activating the integrin-linked kinase and focal adhesion kinase (ILK\/FAK)-signaling axis. These findings are especially noteworthy in truncated O-glycan (Tn and STn antigen)-expressing PDAC cells. Activation of these oncogenic-signaling pathways resulted in part from interactions between MUC16 and integrin complexes (\u03b14\u03b21), which showed a stronger association with aberrant glycoforms of MUC16. Using a monoclonal antibody to functionally hinder MUC16 significantly reduced the migratory cascades in our model. Together, these findings suggest that truncated O-glycan containing MUC16 exacerbates malignancy in PDAC by activating FAK signaling through specific interactions with \u03b14 and \u03b21 integrin complexes on cancer cell membranes. Targeting these aberrant glycoforms of MUC16 can aid in the development of a novel platform to study and treat metastatic pancreatic cancer.<\/jats:p>","DOI":"10.3390\/ijms23105459","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T09:27:56Z","timestamp":1652520476000},"page":"5459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via \u03b14\u03b21 Integrin Complexes and FAK Signaling"],"prefix":"10.3390","volume":"23","author":[{"given":"Christabelle","family":"Rajesh","sequence":"first","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Sagar","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"Rathinavel","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya Thomas","family":"Chemparathy","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlu Laura","family":"Peng","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514-7295, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen Jen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514-7295, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Hollingsworth","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"},{"name":"Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-1630","authenticated-orcid":false,"given":"Prakash","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"},{"name":"Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJM198310133091503","article-title":"A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer","volume":"309","author":"Bast","year":"2010","journal-title":"N. 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