We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Truncated O-Glycan-Bearing MUC16 Enhances Pancreatic Cancer Cells Aggressiveness via α4β1 Integrin Complexes and FAK Signaling.
- Authors
Rajesh, Christabelle; Sagar, Satish; Rathinavel, Ashok Kumar; Chemparathy, Divya Thomas; Peng, Xianlu Laura; Yeh, Jen Jen; Hollingsworth, Michael A.; Radhakrishnan, Prakash
- Abstract
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 (α4β1), 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 α4 and β1 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.
- Subjects
PANCREATIC cancer; FOCAL adhesion kinase; CANCER cells; CELL migration; PANCREATIC duct; INTEGRINS
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 10, p5459
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23105459