Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Chang, Wei Chun; Cheng, Wei; Cheng, Bi Hua; Chen, Lumin; Ju, Li Jing; Ou, Yu Jer; Jeng, Long Bin; Yang, Mei; Hung, Yao Ching; Lung, Wen

doi:10.1002/cam4.1295

Cited by 36 publications

(36 citation statements)

References 42 publications

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“…Downregulation of ACSS3 significantly suppressed the growth of BLCA cells in vitro and in vivo. Indeed, previous report uncovered a higher expression of ACSS3 in tumor comparing to normal parental lesions and downregulation of ACSS3 inhibits progression of gastric cancer 13 . In hepatocellular carcinoma, ACSS3 was expressed in mitochondria and specifically recognized a subtype of hepatocellular carcinoma (namely iHCC2, which represents poor clinical survival rate) 9 , suggesting that the presence of ACSS3 may be noxious in hepatocellular carcinoma as well.…”

Section: Discussionmentioning

confidence: 92%

“…On the other hand, little is known about the function of newly identified ACSS member, ACSS3. It has been proposed that ACSS3 acts as an important prognosis biomarker in gastric cancer 13 and ACSS3 serves as a biomarker to stratify subtypes of hepatocellular carcinoma 9 . However, the biological function of ACSS3 has not been verified in cancer cells yet.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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Cancer cells adapt to nutrient-deprived tumor microenvironment during progression via regulating the level and function of metabolic enzymes. Acetyl-coenzyme A (AcCoA) is a key metabolic intermediate that is crucial for cancer cell metabolism, especially under metabolic stress. It is of special significance to decipher the role acetyl-CoA synthetase short chain family (ACSS) in cancer cells confronting metabolic stress. Here we analyzed the generation of lipogenic AcCoA in bladder cancer cells under metabolic stress and found that in bladder urothelial carcinoma (BLCA) cells, the proportion of lipogenic AcCoA generated from glucose were largely reduced under metabolic stress. Our results revealed that ACSS3 was responsible for lipogenic AcCoA synthesis in BLCA cells under metabolic stress. Interestingly, we found that ACSS3 was required for acetate utilization and histone acetylation. Moreover, our data illustrated that ACSS3 promoted BLCA cell growth. In addition, through analyzing clinical samples, we found that both mRNA and protein levels of ACSS3 were dramatically upregulated in BLCA samples in comparison with adjacent controls and BLCA patients with lower ACSS3 expression were entitled with longer overall survival. Our data revealed an oncogenic role of ACSS3 via regulating AcCoA generation in BLCA and provided a promising target in metabolic pathway for BLCA treatment.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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“…Several genes were down-regulated in primary PC compared to benign tissues, and almost all were further down-regulated in the progression to metastatic disease—EVA1C, ACSS3, C15orf41, PARM1, EYA4, GSTM2 and GSTP1 (MAM 1, 2 and 7, Figure 3 B). EVA1C has not previously been reported in cancer, but ACSS3 is a marker for gastric cancer [ 40 ]. PARM1 is androgen regulated, with a role in cell proliferation [ 59 ].…”

Section: Resultsmentioning

confidence: 99%

The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis

Marzec

Ross-Adams

Pirro

et al. 2021

Cancers

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Next-generation sequencing of primary tumors is now standard for transcriptomic studies, but microarray-based data still constitute the majority of available information on other clinically valuable samples, including archive material. Using prostate cancer (PC) as a model, we developed a robust analytical framework to integrate data across different technical platforms and disease subtypes to connect distinct disease stages and reveal potentially relevant genes not identifiable from single studies alone. We reconstructed the molecular profile of PC to yield the first comprehensive insight into its development, by tracking changes in mRNA levels from normal prostate to high-grade prostatic intraepithelial neoplasia, and metastatic disease. A total of nine previously unreported stage-specific candidate genes with prognostic significance were also found. Here, we integrate gene expression data from disparate sample types, disease stages and technical platforms into one coherent whole, to give a global view of the expression changes associated with the development and progression of PC from normal tissue through to metastatic disease. Summary and individual data are available online at the Prostate Integrative Expression Database (PIXdb), a user-friendly interface designed for clinicians and laboratory researchers to facilitate translational research.

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“…Furthermore, silencing of ACSS2 in mouse models of liver cancer leads to dramatic reduction of tumor growth [ 63 ]. Recently, expression of ACSS3 has also been reported in association with cancer growth and invasion in human gastric cancer and bladder urothelial carcinoma [ 64 , 65 ]. All these data indicate that ACSS3 may represent an interesting candidate for tumorigenesis of CJM and that p.P532S could act as an activating driver mutation.…”

Section: Resultsmentioning

confidence: 99%

Genomic and transcriptomic landscape of conjunctival melanoma

et al. 2020

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Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM.

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Mitochondrial Acetyl‐CoA Synthetase 3 is Biosignature of Gastric Cancer Progression

Cited by 36 publications

References 42 publications

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

The Transcriptomic Landscape of Prostate Cancer Development and Progression: An Integrative Analysis

Genomic and transcriptomic landscape of conjunctival melanoma

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