AI Article Synopsis
- DNAJB9 is a heat shock protein that helps maintain protein function and cellular balance, but its role in cancer is not fully understood.
- Restoration of DNAJB9 was found to reduce migration, invasion, and metastasis in triple-negative breast cancer (TNBC) cells by stabilizing FBXO45 and decreasing ZEB1 levels, which helps prevent a process called epithelial-mesenchymal transition (EMT).
- Lower levels of DNAJB9 and FBXO45 in breast cancer tissues are linked to worse patient outcomes, suggesting that targeting the DNAJB9-FBXO45 pathway could offer new therapeutic options for aggressive cancers.
Article Abstract
DNAJB9, a member of the heat shock protein 40 family, acts as a multifunctional player involved in the maintenance of their client proteins and cellular homeostasis. However, the mechanistic action of DNAJB9 in human malignancies is yet to be fully understood. In this study, we found that ectopic restoration of DNAJB9 inhibits the migration, invasion, in vivo metastasis, and lung colonization of triple-negative breast cancer (TNBC) cells. Mechanistically, DNAJB9 stabilizes FBXO45 protein by suppressing self-ubiquitination and reduces the abundance of ZEB1 by Lys48-linked polyubiquitination to inhibit the epithelial-mesenchymal transition (EMT) and metastasis. Clinically, the reduction of DNAJB9 expression, concomitant with decreased FBXO45 abundance in breast cancer tissues, correlates with poorer clinical outcomes of patients with breast cancer. Taken together, our results provide a novel insight into the metastasis of TNBC and define a promising therapeutic strategy for cancers with overactive ZEB1 by regulating the DNAJB9-FBXO45 signaling axis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106677 | PMC |
| http://dx.doi.org/10.1038/s41419-021-03757-x | DOI Listing |
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