LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control

Gan, Wenjian; Dai, Xiaoming; Dai, Xiangpeng; Xie, Jun; Yin, Shasha; Zhu, Jun‐Jie; Wang, Chen; Liu, Yuchen; Guo, Jianping; Wang, Min; Liu, Jing; Hu, Jia; Quinton, Ryan J.; Ganem, Neil J.; Liu, Pengda; Asara, John M.; Pandolfi, Pier Paolo; Yang, Yingzi; He, Zhigang; Gao, Guangping

doi:10.1038/s41556-020-0463-6

Cited by 70 publications

(60 citation statements)

References 41 publications

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“…Thus, for both mTORC1 and mTORC2, it has been shown to positively regulate YAP stabilisation and signalling [110][111][112] , while different components of the Hippo pathway have been marked as regulating points of mTORC1. A recent report of Gan and coworkers 113 showed that LATS1/2 suppresses mTORC1 activity by phosphorylation of S606 Raptor, and consequently preventing Raptor-Rheb interconnection. Similarly, NF2-deficient human meningioma cells and NF2-KD arachnoidal cells show rapamycin-sensitive constitutive mTORC1 activation 114 .…”

Section: Hippo Pathway and Mtorc1mentioning

confidence: 99%

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

et al. 2020

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Contextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.

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Section: Hippo Pathway and Mtorc1mentioning

confidence: 99%

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

et al. 2020

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“…Recently, a group discovered the Hippo pathway component LATS1/2 kinase phosphorylate Raptor on Ser 606. [ 226 ]. LATS1/2 phosphorylation of Ser 606 induced suppression mTORC1 was suggested to result in a decreased organ size in mice.…”

Section: Mtorc1 Phosphorylation and Regulationmentioning

confidence: 99%

Regulation of mTORC1 by Upstream Stimuli

Melick

Jewell

2020

Genes

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The mammalian target of rapamycin (mTOR) is an evolutionary conserved Ser/Thr protein kinase that senses multiple upstream stimuli to control cell growth, metabolism, and autophagy. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1). A significant amount of research has uncovered the signaling pathways regulated by mTORC1, and the involvement of these signaling cascades in human diseases like cancer, diabetes, and ageing. Here, we review advances in mTORC1 regulation by upstream stimuli. We specifically focus on how growth factors, amino acids, G-protein coupled receptors (GPCRs), phosphorylation, and small GTPases regulate mTORC1 activity and signaling.

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“…For example, phosphorylation of Raptor at Ser606 results in attenuation of mTORC1 kinase activity. The consequence of this is inhibition of glycolysis and lipid biometabolism [64]. Interestingly, mTORC1 is a therapeutic target in PC and a recent study demonstrated that DEPTOR, whose phosphorylation by LATS promotes its inhibitory association with mTORC1, is reduced in PC at both the protein and mRNA levels [65].…”

Section: Post-translation Repression Of Lats1/2mentioning

confidence: 99%

Targeting the Hippo Pathway in Prostate Cancer: What’s New?

Coffey

2021

Cancers

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Identifying novel therapeutic targets for the treatment of prostate cancer (PC) remains a key area of research. With the emergence of resistance to androgen receptor (AR)-targeting therapies, other signalling pathways which crosstalk with AR signalling are important. Over recent years, evidence has accumulated for targeting the Hippo signalling pathway. Discovered in Drosophila melanogasta, the Hippo pathway plays a role in the regulation of organ size, proliferation, migration and invasion. In response to a variety of stimuli, including cell–cell contact, nutrients and stress, a kinase cascade is activated, which includes STK4/3 and LATS1/2 to inhibit the effector proteins YAP and its paralogue TAZ. Transcription by their partner transcription factors is inhibited by modulation of YAP/TAZ cellular localisation and protein turnover. Trnascriptional enhanced associate domain (TEAD) transcription factors are their classical transcriptional partner but other transcription factors, including the AR, have been shown to be modulated by YAP/TAZ. In PC, this pathway can be dysregulated by a number of mechanisms, making it attractive for therapeutic intervention. This review looks at each component of the pathway with a focus on findings from the last year and discusses what knowledge can be applied to the field of PC.

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LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control

Cited by 70 publications

References 41 publications

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

Regulation of mTORC1 by Upstream Stimuli

Targeting the Hippo Pathway in Prostate Cancer: What’s New?

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