Snail suppresses cellular senescence and promotes fibroblast‐led cancer cell invasion

Furuya, Satoshi; Endo, Kaori; Takahashi, Akiko; Miyazawa, Keiji; Saitoh, Masao

doi:10.1002/2211-5463.12300

Cited by 17 publications

(20 citation statements)

References 37 publications

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“…The expression of downstream proteins, such as Snail, Bcl-xL, Bcl2, and STAT3, was also induced in NecB-treated old HDFs. Snail is a zinc finger transcription factor that induces cell movement and survival [41] and regulates cellular senescence in IMR90 normal fibroblast cells [42]. The activated YY1 may be recruited to the antioxidant responsive elements (AREs) binding site and then amplified the NRF2-mediated ARE transcription and subsequent cell protection against oxidative damage [43].…”

Section: Discussionmentioning

confidence: 99%

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Jang

Yang

et al. 2019

Aging

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Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser 15 phosphorylated p53, caveolin-1, p21 waf1 , p16 ink4a , p27 kip1 , and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1−5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro , reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan.

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Section: Discussionmentioning

confidence: 99%

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Jang

Yang

et al. 2019

Aging

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“…Docetaxel and Erlotinib were from Pepro Tech (Rocky Hill, NJ) and Wako (Osaka, Japan), respectively. The human Slug and human Snail expression plasmids were described previously [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Reciprocal expression of Slug and Snail in human oral cancer cells

et al. 2018

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Snail, also called Snai1, is a key regulator of EMT. Snail plays crucial roles in cancer progression, including resistance to anti-tumor drugs and invasion by various cancer cells. Slug, also known as Snai2, is also involved in the aggravation of certain tumors. In this study, we examined the roles of Slug in human oral squamous cell carcinoma (OSCC) cells. Slug is highly expressed in these cells, and Slug siRNA effectively represses anti-tumor drug resistance and invasive properties. In addition, transforming growth factor (TGF)-β upregulates the expression of Snail and Slug and promotes resistance to anti-tumor drugs in OSCC cells. Surprisingly, Slug siRNA appears to upregulate Snail expression considerably in OSCC cells. Snail siRNA also appears to upregulate Slug expression. Thus, either Slug or Snail siRNA alone partially mitigates malignant phenotypes in the presence of TGF-β, whereas both Slug and Snail siRNAs together dramatically suppress them. Therefore, Slug and Snail in tandem, but not alone, are potential therapeutic targets for nucleic acid medicines to treat oral cancer.

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“…Interestingly, Snail, ZEB, and Twist confer resistance to senescence and prevent oncogene-induced senescence and replicative senescence in cancers. Snail inhibits oncogene-induced senescence by decreasing p16INK4a expression, thereby helping premalignant cells to escape the oncogene-induced senescence, which acts as a tumorigenesis barrier [192, 193].…”

Section: Emtmentioning

confidence: 99%

Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype

Lee

Jeon

et al. 2018

Oxidative Medicine and Cellular Longevity

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Metastasis is a major obstacle to the efficient and successful treatment of cancer. Initiation of metastasis requires epithelial-mesenchymal transition (EMT) that is regulated by several transcription factors, including Snail and ZEB1/2. EMT is closely linked to the acquisition of cancer stem cell (CSC) properties and chemoresistance, which contribute to tumor malignancy. Tumor suppressor p53 inhibits EMT and metastasis by negatively regulating several EMT-inducing transcription factors and regulatory molecules; thus, its inhibition is crucial in EMT, invasion, metastasis, and stemness. Metabolic alterations are another hallmark of cancer. Most cancer cells are more dependent on glycolysis than on mitochondrial oxidative phosphorylation for their energy production, even in the presence of oxygen. Cancer cells enhance other oncogenic metabolic pathways, such as glutamine metabolism, pentose phosphate pathway, and the synthesis of fatty acids and cholesterol. Metabolic reprogramming in cancer is regulated by the activation of oncogenes or loss of tumor suppressors that contribute to tumor progression. Oncogenic metabolism has been recently linked closely with the induction of EMT or CSC phenotypes by the induction of several metabolic enzyme genes. In addition, several transcription factors and molecules involved in EMT or CSCs, including Snail, Dlx-2, HIF-1α, STAT3, TGF-β, Wnt, and Akt, regulate oncogenic metabolism. Moreover, p53 induces metabolic change by directly regulating several metabolic enzymes. The collective data indicate the importance of oncogenic metabolism in the regulation of EMT, cell invasion and metastasis, and adoption of the CSC phenotype, which all contribute to malignant transformation and tumor development. In this review, we highlight the oncogenic metabolism as a key regulator of EMT and CSC, which is related with tumor progression involving metastasis and chemoresistance. Targeting oncometabolism might be a promising strategy for the development of effective anticancer therapy.

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Snail suppresses cellular senescence and promotes fibroblast‐led cancer cell invasion

Cited by 17 publications

References 37 publications

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Reciprocal expression of Slug and Snail in human oral cancer cells

Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype

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