Sulforaphane reduces YAP/∆Np63α signaling to reduce cancer stem cell survival and tumor formation

Fisher, Mike; Ciavattone, Nicholas; Grun, Daniel; Adhikary, Gautam; Eckert, Richard L.

doi:10.18632/oncotarget.20562

Cited by 37 publications

(34 citation statements)

References 41 publications

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“…In that study, ΔNp63 and AKT inhibition were shown to modulate YAP1. Recent studies indicate that the function or stability of ΔNp63 and YAP1 can be disrupted by natural isothiocynates such as sulforaphane, and by digitoxin, indicating potential as targets for chemoprevention or therapy (Fisher et al, 2017; Huang et al, 2017). We discovered that predominant expression of ΔNp63 isoforms and embedded miR-944 by SCC is correlated with decreased methylation of CpGs at the alternative TSS compared to those of the TSS for the TAp63 isoforms.…”

Section: Discussionmentioning

confidence: 99%

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Campbell¹,

Yau²,

Bowlby³

et al. 2018

Cell Reports

256

275

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SUMMARY This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Campbell¹,

Yau²,

Bowlby³

et al. 2018

Cell Reports

256

275

View full text Add to dashboard Cite

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“…SFN was shown to suppress tumor angiogenesis by reducing cell viability, migration and tube formation in HUVEC-epithelial cell lines possibly through inhibition of signalling between STAT3/HIF-1α/VEGF [118]. It was recently shown to reduce YAP1 signaling leading to a reduction in cancer stem cell survival and tumor formation in epidermal squamous cell carcinoma [121].…”

Section: Sulforaphane (Sfn)mentioning

confidence: 99%

The Power of Phytochemicals Combination in Cancer Chemoprevention

Rizeq¹,

Gupta²,

Ilesanmi³

et al. 2020

J. Cancer

101

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Conventional therapies for cancer treatment have posed many challenges, including toxicity, multidrug resistance and economic expenses. In contrast, complementary alternative medicine (CAM), employing phytochemicals have recently received increased attention owing to their capability to modulate a myriad of molecular mechanisms with a less toxic effect. Increasing evidence from preclinical and clinical studies suggest that phytochemicals can favorably modulate several signaling pathways involved in cancer development and progression. Combinations of phytochemicals promote cell death, inhibit cell proliferation and invasion, sensitize cancerous cells, and boost the immune system, thus making them striking alternatives in cancer therapy. We previously investigated the effect of six phytochemicals (Indol-3-Carbinol, Resveratrol, C-phycocyanin, Isoflavone, Curcumin and Quercetin), at their bioavailable levels on breast cancer cell lines and were compared to primary cell lines over a period of 6 days. This study showed the compounds had a synergestic effect in inhibiting cell proliferation, reducing cellular migration and invasion, inducing both cell cycle arrest and apoptosis. Despite the vast number of basic science and preclinical cancer studies involving phytochemicals, the number of CAM clinical trials in cancer treatment still remains nascent. In this review, we summarize findings from preclinical and clinical studies, including our work involving use of phytochemicals, individually as well as in combination and further discuss the potential of these phytochemicals to pave way to integrate CAM in primary health care.

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“…In the prevention of squamous cell carcinoma yes-associated protein 1 (YAP1) and ∆Np63α are an important target of SFN. Tumor cell growth inhibition was highly correlated with the downregulation of YAP1 and ∆Np63α [ 121 ]. YAP1 is involved with the cell proliferation and suppressing apoptotic genes.…”

Section: Molecular Mechanism Of Itcs In Cancer Preventionmentioning

confidence: 99%

Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers

2018

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Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer.

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Sulforaphane reduces YAP/∆Np63α signaling to reduce cancer stem cell survival and tumor formation

Cited by 37 publications

References 41 publications

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

The Power of Phytochemicals Combination in Cancer Chemoprevention

Anti-Carcinogenic Glucosinolates in Cruciferous Vegetables and Their Antagonistic Effects on Prevention of Cancers

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