Loss of ZDHHC-Mediated Scribble Palmitoylation Disrupts Cell Polarity and Promotes Prostate Cancer Progression
Abstract
Progression and metastasis of prostate cancers (PCs) are major therapeutic challenges, with the underlying mechanisms remaining unclear. The rise of AR-negative neuroendocrine prostate cancer (NEPC) cells is recently recognized as a major mechanism. The apical-basal polarity of epithelial cells plays critical roles in regulating normal cell migration and proliferation in prostate. Loss of cell polarity leads to tissue disorganization, uncontrolled proliferation and migration, hallmarks of prostate cancer progression and metastasis. ZDHHC7-mediated palmitoylation of Scribble is critical for cell polarity and metastasis. In the second year of the study, we found that loss of ZDHHC7 is significant in NEPC samples. We have generated ZDHHC7 knockout cell lines with various prostate cancer progression stages. We found that loss of ZDHHC7 led to loss of SCRIB palmitoylation, and activation of YAP signaling, and up-regulation of NEPC markers. We will further test the hypothesis that ZDHHC7loss and SCRIB depalmitoylation contributes to prostate cancer cell progression through converting castration-resistant prostate cancer cells to NEPC phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2020
- Accession Number
- AD1110043
Entities
People
- Xu Wu
Organizations
- Massachusetts General Hospital
- Northwestern University