Author Correction: A census of pathway maps in cancer systems biology

Kuenzi, Brent M.; Ideker, Trey

doi:10.1038/s41568-021-00331-7

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor-suppressive Hippo/Yap signaling pathway has attracted attention following reports that inhibits tumorigenesis (124)(125)(126). Activation of the Hippo/Yap signaling pathway primarily involves tumor suppressors (the Mst1/2 kinase cascade) and the following downstream regulators: following downstream regulators: Yap, transcriptional coactivator with PDZ postsynaptic density protein (TAZ), Drosophila disk large tumor suppressor and zonula occludens-1 protein-binding motif (127).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Meng

Nguyen

et al. 2022

Mol Med Rep

View full text Add to dashboard Cite

colorectal cancer (crc) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product-derived and chemotherapy agents including curcumin combined with 5-fluorouracil, resveratrol combined with cisplatin and epigallocatechin-3-gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of ua and doX on the cell proliferation, apoptosis, migration and cell cycle of CRC cells were investigated by performing Cell proliferation assay, a soft agar colony formation assay, flow cytometry, wound healing assay and western blotting assay. Subsequently, the expression of AKT and Hippo signaling pathway-associated proteins were also assessed by western blot assay. Moreover, a xenograft nude mouse model was constructed to verify the effects of UA and doX on the tumorigenesis of HcT116 cell in vivo. The present study reported that ursolic acid (UA) strongly enhanced the antitumor action of doxorubicin (DOX) via blocking the akt/glycogen synthase kinase-3β (Gsk3β) signaling pathway and activating tumor-suppressive Hippo signaling (mammalian Ste20-like kinase 1 and 2, salvador family WW domain containing protein 1 and MOB kinase activator 1), thereby downregulating downstream effector yes-associated protein 1 (Yap) and connective tissue growth factor (cTGF) protein expression levels in CRC cells. Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway-associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas akt activator Sc79 exerted an opposite effect in cTGF expression. In vivo, treatment with UA combined with DOX markedly suppressed the progression of CRC without any toxic effects on a xenograft mouse model by disrupting Akt signaling and activating the Hippo signaling pathway. These results demonstrated that UA and DOX treatment successfully induced akt/Gsk3β inactivation via Hippo signaling pathway activation to promote Yap degradation, resulting in the inhibition of colorectal tumorigenesis. In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

show abstract