PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence Journal Article
| Authors: | Klein, M. E.; Dickson, M. A.; Antonescu, C.; Qin, L. X.; Dooley, S. J.; Barlas, A.; Manova, K.; Schwartz, G. K.; Crago, A. M.; Singer, S.; Koff, A.; Tap, W. D. |
| Article Title: | PDLIM7 and CDH18 regulate the turnover of MDM2 during CDK4/6 inhibitor therapy-induced senescence |
| Abstract: | CDK4/6 inhibitors are being used to treat a variety of human malignancies. In well-differentiated and dedifferentiated liposarcoma their clinical promise is associated with their ability to downregulate the MDM2 protein. The downregulation of MDM2 following treatment with CDK4/6 inhibitors also induces many cultured tumor cell lines derived from different types of malignancies to progress from quiescence into senescence. Here we used cultured human cell lines and defined a role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells. Materials from our previous phase II trials with palbociclib were then used to demonstrate that expression of CDH18 protein was associated with response, measured as both progression-free survival and overall survival. This supports the hypothesis that the biologic transition from quiescence to senescence has clinical relevance for this class of drugs. © 2018, The Author(s). |
| Journal Title: | Oncogene |
| Volume: | 37 |
| Issue: | 37 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-09-13 |
| Start Page: | 5066 |
| End Page: | 5078 |
| Language: | English |
| DOI: | 10.1038/s41388-018-0332-y |
| PROVIDER: | scopus |
| PMCID: | PMC6137027 |
| PUBMED: | 29789718 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2018 -- Source: Scopus |
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