Loss of ZDHHC-Mediated Scribble Palmitoylation Disrupts Cell Polarity and Promotes Prostate Cancer Progression
Technical Report,15 Jul 2018,14 Jul 2019
Massachusetts General Hospital Boston United States
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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 ZDHHC7 loss and SCRIB depalmitoylation contributes to prostate cancer cell progression through converting castration-resistant prostate cancer cells to NEPC phenotype.
- Medicine and Medical Research
- Anatomy and Physiology