Targeting mTOR for cancer therapy

Hua, Hui; Kong, Qingbin; Zhang, Hongying; Wang, Jiao; Luo, Ting; Jiang, Yangfu

doi:10.1186/s13045-019-0754-1

Cited by 690 publications

(514 citation statements)

References 232 publications

(265 reference statements)

Supporting

Mentioning

502

Contrasting

Unclassified

Order By: Relevance

“…Oncogenes that displayed both aberrant methylation and increased expression included MTOR and NOTCH1 (Tables S6 and S10). MTOR encodes a protein kinase promoting cell growth and survival via PI3K/AKT/mTOR signaling [27], and our data suggest that this pathway could also be involved in ATC cases lacking activating mutations in these genes. Considering that clinical trials are ongoing for mTOR inhibitors in ATC [28], the role of epigenetic activation of MTOR should be further explored in larger ATC cohorts.…”

Section: Discussionmentioning

confidence: 68%

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

Ravi

Yang

Mylona

et al. 2020

Cancers

View full text Add to dashboard Cite

Anaplastic thyroid cancer (ATC) is one of the most malignant tumors, with a median survival of only a few months. The tumorigenic processes of this disease have not yet been completely unraveled. Here, we report an mRNA expression and DNA methylation analysis of fourteen primary ATCs. ATCs clustered separately from normal thyroid tissue in unsupervised analyses, both by RNA expression and by DNA methylation. In expression analysis, enrichment of cell-cycle-related genes as well as downregulation of genes related to thyroid function were seen. Furthermore, ATC displayed a global hypomethylation of the genome but with hypermethylation of CpG islands. Notably, several cancer-related genes displayed a correlation between RNA expression and DNA methylation status, including MTOR, NOTCH1, and MAGI1. Furthermore, TSHR and SLC26A7, encoding the thyroid-stimulating hormone receptor and an iodine receptor highly expressed in normal thyroid, respectively, displayed low expression as well as aberrant gene body DNA methylation. This study is the largest investigation of global DNA methylation in ATC to date. It shows that aberrant DNA methylation is common in ATC and likely contributes to tumorigenesis in this disease. Future explorations of novel treatments should take this into consideration.Cancers 2020, 12, 680 2 of 11 to display promoter hypermethylation in ATC include PTEN, RAP1GAP, RASAL1, REC8, RASSF1,, whereas hypomethylation has been observed in NOTCH4, MAP17, and TCL1B. Notably, TSHR and NKX2-1 (previously TTF-1), involved in thyroid functions, have also been reported to be hypermethylated in ATC [17,18].Matched expression and methylation data may unravel genes that are dysregulated by methylation and that could contribute to tumorigenesis. However, no such studies have hitherto been performed on the genomic level in ATC. Here, we applied RNA sequencing (RNA-seq) and genome-wide methylation arrays, including 850,000 CpG sites, on primary ATC tumor samples to identify novel genes that exhibit significant methylation and expression correlation and to further delineate the tumorigenic process of ATC.

show abstract

Section: Discussionmentioning

confidence: 68%

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

Ravi

Yang

Mylona

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…mTOR deregulation occurs in many human pathologies, including cancer, metabolic diseases, nervous system diseases, and inflammation 49,50 . There are already many mTOR inhibitors for the treatment of human cancer, and many more have been evaluated in clinical trials [51][52][53][54][55] . mTOR activates glycolysis through modulating the expression of the transcription factor HIF-1α, indirectly upregulating the transcription of almost all glycolytic genes in tumor cell 5,28,56 .…”

Section: Discussionmentioning

confidence: 99%

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

et al. 2020

View full text Add to dashboard Cite

Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/ HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.

show abstract

“…The mammalian target of rapamycin (mTOR) is a type of protein kinase which regulates cell metabolism, proliferation, and growth. The activation of PI3K/Akt pathway results in the aberrant activation of mTOR in most cancer cells [97,193,194]. It is known that mTOR controls the expression of many survival proteins via activating p70 S6 kinase (S6K) and inhibition of eIF4E inhibitor 4E-BP1 [193].…”

Section: Mammalian Target Of Rapamycin (Mtor)mentioning

confidence: 99%

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Ong

Lee

Tang

et al. 2019

Cancers

131

View full text Add to dashboard Cite

Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial-mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5 AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

show abstract

Targeting mTOR for cancer therapy

Cited by 690 publications

References 232 publications

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

Global RNA Expression and DNA Methylation Patterns in Primary Anaplastic Thyroid Cancer

Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Contact Info

Product

Resources

About