YAP/TAZ-mediated activation of serine metabolism and methylation regulation is critical for LKB1-deficient breast cancer progression

Wu, Qi; Li, Juanjuan; Sun, Si; Chen, Xinyue; Zhang, Hanpu; Li, Bei; Sun, Shengrong

doi:10.1042/bsr20171072

Cited by 28 publications

(22 citation statements)

References 40 publications

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“…Indeed, aerobic glycolysis, mevalonate synthesis, Liver Kinase B1 (LKB1), 5’ AMP-activated Protein Kinase (AMPK), salt-inducible kinases, and the Tuberous Sclerosis-mammalian Target of Rapamycin complex (TSC-mTOR) all influence YAP/TAZ activity [ 209 , 321 , 322 , 323 , 324 , 325 ]. Importantly, activation of YAP and TAZ by some of these metabolic pathways promotes tumorigenesis and drives cancer progression [ 155 , 322 , 324 , 326 , 327 ]. Two other pathways that have established roles in cancer development, progression, and metastasis, and have been linked to the Hippo-YAP/TAZ pathway are the TGFβ and Wnt/β-catenin pathways.…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Warren

Xiao

2018

Cancers

133

125

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Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease. To this end, we also discuss several potential strategies for inhibiting YAP/TAZ activation in cancer and the challenges each strategy poses.

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Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Warren

Xiao

2018

Cancers

133

125

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“…YAP gene amplification specifically existed in TNBC, not in estrogen receptor alpha positive breast cancer (https:// www.cbioportal.org). Besides, depletion of YAP in TNBC cell lines inhibited cell invasion and proliferation in both in vitro and in vivo 3,[15][16][17] . All these studies indicated that Hippo activation is an important driving force for TNBC progression.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187

Wang

Kong

et al. 2020

Oncogenesis

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Breast cancer is the most common malignancy for women worldwide, while Triple Negative Breast Cancer (TNBC) accounts for 20% in all patients. Compared with estrogen receptor positive breast cancer, which could be effectively controlled via endocrine therapy, TNBC is more aggressive and worse in prognosis. It is therefore urgent and necessary to develop a novel therapeutic strategy for TNBC treatment. Recent studies identified Hippo signaling is highly activated in TNBC, which could be a driving pathway for TNBC progression. In our study, we determine RNF187 as a negative regulator for Hippo signaling activation. RNF187 depletion significantly decreases cell migration and invasion capacity in TNBC. These effects could be rescued by further YAP depletion. Depletion of RNF187 increases the YAP protein level and Hippo signaling target genes, such as CTGF and CYR61 in TNBC. Immuno-precipitation assay shows that RNF187 associates with YAP, promoting its degradation possibly via inducing YAP K48-dependent polyubiquitination. Interestingly, Our clinical data reveals that RNF187 reversely correlates with YAP protein level and Hippo target genes. RNF187 tends to correlate with good prognosis in TNBC patients. Our study provides evidence to establish a proteolytic mechanism in regulation Hippo signaling activation in TNBC.

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“…Recent studies have shown that transcriptional regulation and epigenetic regulation are critical for the autophagic process 18 . Mutations in core enzymes associated with one‐carbon metabolism and SAM are observed in cancer and are accompanied by aberrant methylation states 19 . SAM is an important metabolite and can act as a nutrition, energy and stress sensor in vivo and in vitro, thus regulating autophagy.…”

Section: Introductionmentioning

confidence: 99%

S‐adenosylmethionine: A metabolite critical to the regulation of autophagy

Ouyang

et al. 2020

Cell Proliferation

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Autophagy is a mechanism that enables cells to maintain cellular homeostasis by removing damaged materials and mobilizing energy reserves in conditions of starvation. Although nutrient availability strongly impacts the process of autophagy, the specific metabolites that regulate autophagic responses have not yet been determined. Recent results indicate that S‐adenosylmethionine (SAM) represents a critical inhibitor of methionine starvation–induced autophagy. SAM is primarily involved in four key metabolic pathways: transmethylation, transsulphuration, polyamine synthesis and 5′‐deoxyadenosyl 5′‐radical–mediated biochemical transformations. SAM is the sole methyl group donor involved in the methylation of DNA, RNA and histones, modulating the autophagic process by mediating epigenetic effects. Moreover, the metabolites of SAM, such as homocysteine, glutathione, decarboxylated SAM and spermidine, also exert important influences on the regulation of autophagy. From our perspective, nuclear‐cytosolic SAM is a conserved metabolic inhibitor that connects cellular metabolic status and the regulation of autophagy. In the future, SAM might be a new target of autophagy regulators and be widely used in the treatment of various diseases.

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YAP/TAZ-mediated activation of serine metabolism and methylation regulation is critical for LKB1-deficient breast cancer progression

Cited by 28 publications

References 40 publications

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187

S‐adenosylmethionine: A metabolite critical to the regulation of autophagy

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