ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition

Guo, Weinan; Ma, Jinyuan; Yang, Yuqi; Guo, Sen; Zhang, Weigang; Zhao, Tao; Yi, Xiuli; Wang, Huina; Wang, Shiyu; Liu, Yu; Dai, Wei; Chen, Xuguang; Shi, Qiong; Wang, Gang; Gao, Tianwen; Li, Chunying

doi:10.1158/1078-0432.ccr-19-1359

Cited by 46 publications

(36 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to participating in lipid metabolism in the cytosol, nucleus-translocated ACLY generates acetyl-CoA for histone acetylation and gene transcription regulation ( Wellen et al, 2009 ). In melanoma cells, ACLY enhances acetyltransferase p300-dependent histone acetylation, thereby promoting PPARγ coactivator (PGC) 1α–mediated mitochondrial biogenesis for cell proliferation ( Guo et al, 2020 ). In PDAC, glioma, and prostate cancer cells, growth factors or oncogenic K-Ras expression promotes AKT–ACLY signaling, histone acetylation, cell proliferation, and tumor growth ( Carrer et al, 2019 ; Lee et al, 2014 ).…”

Section: Lipogenesismentioning

confidence: 99%

Lipid metabolism and cancer

Bian

Meng

et al. 2020

Journal of Experimental Medicine

510

329

View full text Add to dashboard Cite

Dysregulation in lipid metabolism is among the most prominent metabolic alterations in cancer. Cancer cells harness lipid metabolism to obtain energy, components for biological membranes, and signaling molecules needed for proliferation, survival, invasion, metastasis, and response to the tumor microenvironment impact and cancer therapy. Here, we summarize and discuss current knowledge about the advances made in understanding the regulation of lipid metabolism in cancer cells and introduce different approaches that have been clinically used to disrupt lipid metabolism in cancer therapy.

show abstract

Section: Lipogenesismentioning

confidence: 99%

Lipid metabolism and cancer

Bian

Meng

et al. 2020

Journal of Experimental Medicine

510

329

View full text Add to dashboard Cite

show abstract

“…Therefore, ATP1B4 is not only the source gene of TCONS_00279168 but also its target gene. ATP1B4 is a member of ATPase Na+/K+ transporting family, which is believed to contribute to the activity of the MAPK signaling pathway, which is well supported by the studies in humans [ 53 , 54 ]. Furthermore, ATP1B4 , as an important member of ATPase Na+/K+ transporting beta M family, which is involved in the regulation of gene expression level in TGF-β signaling pathway as exemplified by an increase of expression of inhibitory Smad7.…”

Section: Discussionmentioning

confidence: 93%

Analysis of lncRNAs Expression Profiles in Hair Follicle of Hu Sheep Lambskin

Chen

Sun

et al. 2020

Animals

View full text Add to dashboard Cite

Lambskin of the Hu sheep exhibits high economic value due to its water-wave pattern. Wool curvature is the key factor of the pattern types and quality of lambskin, and it is formed by the interaction between dermal papilla cells and hair matrix cells in the hair follicle, which is regulated by various genes and signaling pathways. Herein, three full-sibling pairs of two-day-old healthy lambs (n = 6) were divided into a straight wool group (ST) and small waves group (SM) with three repetitions. RNA-seq was applied to determine the expression profile of mRNAs and lncRNAs in Hu sheep hair follicles. 25 differentially expressed mRNAs and 75 differentially expressed lncRNAs were found between SM and ST. FGF12, ATP1B4, and TCONS_00279168 were probably associated with hair follicle development. Then, Gene Ontology (GO) and KEGG enrichment analysis were implemented for the functional annotation of target genes of differentially expressed lncRNAs. The results showed that many genes, such as FGF12 and ATP1B4, were found enriched in PI3K-Akt signaling, MAPK signaling, and Ras signaling pathway associated with hair follicle growth and development. In addition, the interaction network of differentially expressed lncRNAs and mRNAs showed that a total of 6 differentially expressed lncRNAs were associated with 12 differentially expressed mRNAs, which may be as candidate mRNAs and lncRNAs. TCONS_00279168 may target ATP1B4 and FGF12 to regulate MAPK, PI3K-Akt, Ras signaling pathways involved in the sheep hair follicle development process. These results will provide the basis for exploring hair follicle development.

show abstract

“…Meanwhile, exosomal HSPC111 induced the pre-metastatic niche in liver to promote CRLM. A set of recent studies revealed that the elevation of ACLY expression and activity promotes cancer cell growth and metastasis [42,43] , and phosphorylation of ACLY contributes to cellular acetyl-CoA production and then increases histone acetylation [44] . In our study, we observed exosomal HSPC111 treatment speci cally affected the acetylation of H3K27 in CAFs without affecting acetylation of other histone protein.…”

Section: Discussionmentioning

confidence: 99%

Cancer-Secreted Exosomal HSPC111 Promotes Colorectal Cancer Liver Metastasis By Reprogramming Lipid Metabolism in Cancer-Associated Fibroblasts

Zhang¹,

Wang²,

Zhang³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Metastasis and metabolic deregulation are two of the major hallmarks of cancer. Recent studies have revealed the critical driving role of metabolic reprogramming of tumor cells to promote colorectal cancer (CRC) metastasis. However, little is known about the metabolic alterations of cancer-associated fibroblasts (CAFs) in the pre-metastatic niche and how these changes facilitate CRC metastasis.Methods: Liquid chromatography-mass spectrometry (LC-MS) and Isobaric Tags for Relative and Absolute Quantitation (i-TRAQ) method were performed to identify the comparative metabolites and proteins expression in CAFs treated with exosomes derived from CRC cells, respectively. Tissue Microarray (TMA) was used to evaluate the level of HSPC111 in patient’s primary CRC tissues with or without liver metastasis. Co-immunoprecipitation (Co-IP), RNA-seq, chromatin immunoprecipitation (ChIP) migration and wound healing assay and immunofluorescence staining were employed to explore the expression regulation mechanism of exosomal HSPC111 in CAFs. Xenograft models were used to determine whether exosomal HSPC111 can remolding pre-metastatic niche of CAFs to promote CRC liver metastasis (CRLM) in vivo.Results: Here, we demonstrate that CRC cell-secreted exosomal HSPC111 induces a lipid metabolism reprogramming process in CAFs. Importantly, our results indicate that CRC patients with liver metastasis had significantly high level of HSPC111 in CRC tissues than CRC patients without liver metastasis. Mechanistically, HSPC111 upregulate the level of acetyl-CoA and histone acetylation by phosphorylating of ATP-citrate lyase (ACLY) in CAFs. This lipid metabolism reprogramming in CAFs facilitates CXCL5 secretion in vitro and pre-metastatic niche formation in the liver to promote CRLM in an exosomal HSPC111-dependent manner in vivo. In addition, conditioned medium (CM) from CAFs induce EMT of CRC cells by down-regulating E-cadherin levels and up-regulating Vimentin and Snail levels, which could be abolished by CXCL5-neutralizing antibody and CXCR2 inhibitor navarixin. Moreover, the HSPC111-ACLY association in CAFs was reinforced by CXCL5-CXCR2 axis, further promoting exosomal HSPC111 secretion from CRC cells to form a feedforward regulatory loop.Conclusion: Our present study reveals a novel insight into the pro-metastatic role of lipid metabolism reprogramming in CAFs and suggests the CXCL5-CXCR2 axis may be a promising target for halting CRLM.

show abstract

ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition

Cited by 46 publications

References 43 publications

Lipid metabolism and cancer

Lipid metabolism and cancer

Analysis of lncRNAs Expression Profiles in Hair Follicle of Hu Sheep Lambskin

Cancer-Secreted Exosomal HSPC111 Promotes Colorectal Cancer Liver Metastasis By Reprogramming Lipid Metabolism in Cancer-Associated Fibroblasts

Contact Info

Product

Resources

About