Oncotarget published “A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells” which reported that In this study, the authors show that a new HIPK2 isoform increases TEAD reporter activity in NSCLC cells.
They detected and cloned a novel HIPK2 isoform 3 and found that its forced overexpression promotes TEAD reporter activity in NSCLC cells.
Expressing HIPK2 isoform 3_K228A kinase-dead plasmid failed to increase TEAD reporter activity in NSCLC cells.
Next, they showed that two siRNAs targeting HIPK2 decreased HIPK2 isoform 3 and YAP protein levels in NSCLC cells.
In summary, this Oncotarget study indicates that HIPK2 isoform 3, the main HIPK2 isoform expressed in NSCLC, promotes YAP/TEAD transcriptional activity in NSCLC cells.
This Oncotarget study indicates that HIPK2 isoform 3, the main HIPK2 isoform expressed in NSCLC, promotes YAP/TEAD transcriptional activity in NSCLC cells
Dr. Liang You from The University of California said, “Homeodomain-interacting protein kinase-2 (HIPK2) can either promote or inhibit transcription depending on cellular context.“
HIPK2 is positively associated with cell growth in androgen-receptor-positive prostate cancer cells.
In addition, HIPK2 is transcriptionally regulated by nuclear factor erythroid 2 and HIPK2 knockdown increases the sensitivity to cisplatin in non-small cell lung cancer cells.
These studies suggest that the closest human homolog of Hipk, HIPK2, may have the same role in mammalian cells.
For instance, HIPK2 promotes abundance and activity of YAP in a kinase-dependent fashion in 293T cells.
In this study, the authors focused on analysis of the main HIPK2 isoform expressed in non-small-cell lung cancer, which consists of adenocarcinoma and squamous cell carcinoma.
The You Research Team concluded in their Oncotarget Research Paper, “this study suggests that HIPK2 isoform 3 promotes YAP/TEAD transcriptional activity and it may play an oncogenic role in NSCLC. Our results also suggest that HIPK2 isoform 3 may be a potential therapeutic target for NSCLC.“
Featured image: Analysis of side population, sphere formation and TEAD reporter activity after TBID treatment in NSCLC cell lines. (A) Reduction of side population of human NSCLC A549 and H460 cell lines after TBID treatment. (B) Inhibition of secondary tumorsphere formation by TBID treatment in NSCLC cell lines. (C) TEAD reporter activity decreased in a dose-dependent manner in H460 cell line (p < 0.001, t-test). Error bars indicate standard deviations; ***p ≤ .001. (D) Schematic diagram of the potential differences in YAP/TEAD regulation between HIPK2 isoform 1 and isoform 3. Copyright: © 2021 Dai et al.
Reference: Dai Y., Kyoyama H., Yang Y., Wang Y., Liu S., Wang Y., Mao J., Xu Z., Uematsu K., Jablons D. M., You L. A novel isoform of Homeodomain-interacting protein kinase-2 promotes YAP/TEAD transcriptional activity in NSCLC cells. Oncotarget. 2021; 12: 173-184. Retrieved from https://www.oncotarget.com/article/27871/text/
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