Rapamycin synergizes the cytotoxic effects of MEK inhibitor binimetinib and overcomes acquired resistance to therapy in melanoma cell lines in vitro

Ryabaya, Oxana; Абрамов, И. С.; Khochenkov, Dmitry; Akasov, Roman; Шолина, Н. В.; Prokofieva, Anastasia

doi:10.1007/s10637-021-01089-3

Cited by 4 publications

(1 citation statement)

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“…Rapamycin, an mTORC1-dependent autophagy activator, is an FDA-approved drug that is safe for human use. The antitumor effect of rapamycin has been reported in different types of cancer 49 , 50 . In our study, inhibition of YAP by verteporfin or activation of autophagy by rapamycin suppressed the malignant phenotype of PDAC to some extent both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Autophagy-mediated negative feedback attenuates the oncogenic activity of YAP in pancreatic cancer

Sun¹,

Peng²,

Mao³

et al. 2021

Int. J. Biol. Sci.

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Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy in humans, and new therapeutic targets are urgently needed. Yes-associated protein (YAP) plays a significant role in cancer progression. Autophagy is also closely associated with various human cancers. However, the interplay between YAP and autophagy in PDAC remains poorly understood. In this study, we found that YAP was upregulated and activated in PDAC. Further analysis revealed that there is a YAP-autophagy feedback loop in pancreatic cancer. Mechanistically, YAP activates autophagy by promoting Atg5 transcription via TEAD1-mediated binding, while autophagy negatively regulates YAP through autophagic degradation. The hyperactivation of YAP in PDAC unbalances the YAP-autophagy circuit and promotes cancer progression. Inhibition of autophagy enhances the oncogenic activity of YAP in PDAC. The autophagy activator rapamycin promotes the antitumor effect of verteporfin, a YAP inhibitor. Therefore, our study elucidated the interaction between YAP and autophagy in PDAC and our results suggest that targeting the YAP-autophagy circuit may be a new therapeutic strategy for pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%