Publications by authors named "J Westermarck"
Article Synopsis
- Cancer cells experience significant changes in gene expression and epigenetics, including the abnormal activation of certain tissue-specific genes.
- The RNA helicase DDX4 forms structures similar to germ granules in tumors but not in cultured cancer cells, containing proteins linked to RNA and splicing.
- The absence of DDX4 in cancer cells alters gene expression, reduces cancer growth and invasiveness, and is associated with poorer patient outcomes in certain cancers like head and neck squamous cell carcinoma and advanced prostate cancer.
Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatases, expression of dual-specificity phosphatase DUSP6 was found inhibited in dormant cells, but strongly induced upon regrowth.
View Article and Find Full Text PDFCIP2A coordinates phosphosignaling, mitosis, and the DNA damage response.
Trends Cancer
January 2024
Human cancers share requirements for phosphorylation-dependent signaling, mitotic hyperactivity, and survival after DNA damage. The oncoprotein CIP2A (cancerous inhibitor of PP2A) can coordinate all these cancer cell characteristics. In addition to controlling cancer cell phosphoproteomes via inhibition of protein phosphatase PP2A, CIP2A directly interacts with the DNA damage protein TopBP1 (topoisomerase II-binding protein 1).
View Article and Find Full Text PDFMitochondrial glycolysis and hyperactivity of the phosphatidylinositol 3-kinase-protein kinase B (AKT) pathway are hallmarks of malignant brain tumors. However, kinase inhibitors targeting AKT (AKTi) or the glycolysis master regulator pyruvate dehydrogenase kinase (PDKi) have failed to provide clinical benefits for brain tumor patients. Here, we demonstrate that heterogeneous glioblastoma (GB) and medulloblastoma (MB) cell lines display only cytostatic responses to combined AKT and PDK targeting.
View Article and Find Full Text PDFArticle Synopsis
- Combined inhibition of oxidative phosphorylation (OXPHOS) and glycolysis can trigger a pathway that causes tumor cell death via PP2A signaling.
- Using specific inhibitors for mitochondrial complexes I and III, the study reveals that IACS-010759 (a complex I inhibitor) causes the release of CIP2A from PP2A, leading to the breakdown of CIP2A through autophagy.
- The research identifies that the activation of the PP2A complex with the B56δ subunit is crucial for tumor cell death, while the suppression of cell growth from IACS-010759 treatment does not rely on this specific complex.