ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling

Yu, Shiyi; Zhang, Meng; Huang, Ling; Ma, Zhiyong; Gong, Xue; Li, Weiguang; Zhang, Jun; Chen, Liming; Yu, Zhenghong; Zhao, Weiyong; Liu, Yan

doi:10.18632/aging.102572

Cited by 17 publications

(14 citation statements)

References 40 publications

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“…Rsv acts as a negative regulator of these pathways in breast cancer and other cancer types. On the other hand, high levels of CDH1/E-cadherin [ 57 ] and MAPK3/ERK1 [ 58 ] have been associated with favorable prognoses in breast cancer, and Rsv increases their levels and/or activity in MCF7 cells. Importantly, modulation of these genes may attenuate several mechanisms associated with Doxo resistance in MCF7 including (a) increased drug efflux [ 59 ], (b) cell death resistance (through alterations in ER- α and/or NF- κ B pathways) [ 60 , 61 ], (c) epithelial-to-mesenchymal transition [ 62 ], (d) the enrichment of cancer stem cell-like phenotype [ 60 , 63 ], and (e) autophagy [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Finally, our in silico analysis suggested ERK1 as a putative target of Rsv. In MCF7 cells, ERK1 inhibits cell proliferation via the downregulation of YAP1, a transcriptional coactivator involved in breast carcinogenesis [ 58 ]. Indeed, in breast cancer patients, high levels of ERK1 are associated with good prognoses, positive responses to therapy, and controlled cancer progression [ 58 , 89 ].…”

Section: Discussionmentioning

confidence: 99%

“…In MCF7 cells, ERK1 inhibits cell proliferation via the downregulation of YAP1, a transcriptional coactivator involved in breast carcinogenesis [ 58 ]. Indeed, in breast cancer patients, high levels of ERK1 are associated with good prognoses, positive responses to therapy, and controlled cancer progression [ 58 , 89 ]. Rsv has been previously described as increasing ERK1 in MCF7 cells [ 90 , 91 ].…”

Section: Discussionmentioning

confidence: 99%

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Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model

Vargas

Puga

Lenz

et al. 2020

Oxidative Medicine and Cellular Longevity

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Doxorubicin (Doxo) is the most effective chemotherapeutic agent for the treatment of breast cancer. However, resistance to Doxo is common. Adjuvant compounds capable of modulating mechanisms involved in Doxo resistance may potentiate the effectiveness of the drug. Resveratrol (Rsv) has been tested as an adjuvant in mammary malignancies. However, the cellular and molecular mechanisms underlying the effects of cotreatment with Doxo and Rsv in breast cancer are poorly understood. Here, we combined in vitro and in silico analysis to characterize these mechanisms. In vitro, we employed a clinically relevant experimental design consisting of acute (24 h) treatment followed by 15 days of analysis. Acute Rsv potentiated the long-lasting effect of Doxo through the induction of apoptosis and senescence. Cells that survived to the cotreatment triggered high levels of autophagy. Autophagy inhibition during its peak of activation but not concomitant with Doxo+Rsv increased the long-term toxicity of the cotreatment. To uncover key proteins potentially associated with in vitro effects, an in silico multistep strategy was implemented. Chemical-protein networks were predicted based on constitutive gene expression of MCF7 cells and interatomic data from breast cancer. Topological analysis, KM survival analysis, and a quantitative model based on the connectivity between apoptosis, senescence, and autophagy were performed. We found seven putative genes predicted to be modulated by Rsv in the context of Doxo treatment: CCND1, CDH1, ESR1, HSP90AA1, MAPK3, PTPN11, and RPS6KB1. Six out of these seven genes have been experimentally proven to be modulated by Rsv in cancer cells, with 4 of the 6 genes in MCF7 cells. In conclusion, acute Rsv potentiated the long-term toxicity of Doxo in breast cancer potentially through the modulation of genes and mechanisms involved in Doxo resistance. Rational autophagy inhibition potentiated the effects of Rsv+Doxo, a strategy that should be further tested in animal models.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model

Vargas

Puga

Lenz

et al. 2020

Oxidative Medicine and Cellular Longevity

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show abstract

“…The decision to test MAPK1/ERK2 only in the RT-PCR assays was based on reports that show MAPK3/ERK1 association with a better prognosis and its role in modulating the YAP1 signaling pathway, indicating that MAPK3 is a negative regulator of breast cancer development. However, higher expression of MAPK1 predicted a poor prognosis 31 . The studies in the literature agree with our findings showing that TNF-α stimulates the expression of CXCL1 and supports the fact that PGG inhibitory effect over GRO-α/CXCL1 expression through inhibition of NFƙB and MAPK signaling genes may decrease cell proliferation and slow inflammation and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Pentagalloyl glucose inhibits TNF‐α‐activated CXCL1/GRO-α expression and induces apoptosis‐related genes in triple-negative breast cancer cells

Mendonca

Alghamdi

Messeha

et al. 2021

Sci Rep

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In triple-negative breast cancer (TNBC), the tumor microenvironment is associated with increased proliferation, suppressing apoptotic mechanisms, an altered immune response, and drug resistance. The current investigation was designed to examine the natural compound pentagalloyl glucose (PGG) effects on TNF-α activated TNBC cell lines, MDA-MB-231 and MDA-MB-468. The results obtained showed that PGG reduced the expression of the cytokine GRO-α/CXCL1. PGG also inhibited IƙBKE and MAPK1 genes and the protein expression of IƙBKE and MAPK, indicating that GRO-α downregulation is possibly through NFƙB and MAPK signaling pathway. PGG also inhibited cell proliferation in both cell lines. Moreover, PGG induced apoptosis, modulating caspases, and TNF superfamily receptor genes. It also augmented mRNA of receptors DR4 and DR5 expression, which binds to TNF-related apoptosis-induced ligand, a potent and specific stimulator of apoptosis in tumors. Remarkably, PGG induced a 154-fold increase in TNF expression in MDA-MB-468 compared to a 14.6-fold increase in MDA-MB-231 cells. These findings indicate PGG anti-cancer ability in inhibiting tumor cell proliferation and GRO-α release and inducing apoptosis by increasing TNF and TNF family receptors' expression. Thus, PGG use may be recommended as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression.

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“…Another study reported that the loss of FAT atypical cadherin 1 promotes the resistance of estrogen receptor (ER)-positive breast cancer to cyclin-dependent kinase (CDK) 4/6 inhibitors through the accumulation of YAP/TAZ transcription factors on the CDK6 promoter ( 36 ). Similarly, the loss of Ca 2+ -ATPase isoform 2 ( 37 ) and extracellular regulated protein kinase 1 ( 38 ) can activate YAP/TAZ expression. Τhe concept that regular exercise can prevent breast cancer is based on scientific evidence suggesting that the serum levels of catecholamines, including epinephrine and norepinephrine, increase following exercise, thus resulting in YAP1 phosphorylation and its cytoplasmic retention, eventually promoting its tumor suppressive effects ( 39 ).…”

Section: Transcriptional Coactivators Yap/taz As Therapeutic Targets mentioning

confidence: 99%

Hippo/TEAD4 signaling pathway as a potential target for the treatment of breast cancer (Review)

Lin

et al. 2021

Oncol Lett

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Breast cancer is the most common type of cancer among women worldwide. The Hippo signaling pathway is strongly associated with cell proliferation, migration, invasion, metastasis and resistance to breast cancer treatment. The upstream factors involved in the Hippo signaling pathway, including mammalian Ste20 kinases 1/2, large tumor suppressor kinases 1/2 and transcription coactivator Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), have been extensively studied as they are considered therapeutic targets for breast cancer. Recently, it has been suggested that the transcriptional enhancer factor domain (TEAD) family of transcription factors, particularly TEAD4, plays an important role in breast cancer. TEADs interact with YAP/TAZ to act as transcription factors. Notably, recent studies have demonstrated that TEAD4 may also function in a YAP/TAZ-independent manner and serve as a prognostic marker for breast cancer. The present review summarizes the current research on the effect of the aberrant activation of the Hippo signaling pathway on breast cancer progression. Furthermore, the latest advances on the role of the TEAD family in breast cancer are highlighted, and the role of TEAD4 as a potential target for therapeutic intervention in breast cancer is discussed.

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ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling

Cited by 17 publications

References 40 publications

Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model

Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro–In Silico Model

Pentagalloyl glucose inhibits TNF‐α‐activated CXCL1/GRO-α expression and induces apoptosis‐related genes in triple-negative breast cancer cells

Hippo/TEAD4 signaling pathway as a potential target for the treatment of breast cancer (Review)

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