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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Dysregulated YAP1/Hippo Pathway Contributes to Doxorubicin (ADM) Resistance in Acute Myeloid Leukemia (AML)
Yan Song1, Xi Chen1, Rui Huang2
1Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.
Background:
Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).
Methods:
In this study, we established two ADM-resistant cell lines (THP-1/ADM and K562/ ADM). Then, cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real-time PCR was performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot.
Results:
We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM resistance, evidenced by the increased expression in ADMresistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding the role of YAP1 in regulating AML resistance by affecting CSCs characteristics.
Conclusion:
In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM resistance in AML. YAP1 might be a novel biomarker for the treatment of drug resistance in AML.
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