Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

Ebright, Richard Y.; Lee, Sooncheol; Wittner, Ben S.; Niederhoffer, Kira; Nicholson, Benjamin; Bardia, Aditya; Truesdell, Samuel S.; Wiley, Devon F.; Wesley, Benjamin; Li, Selena; Mai, Andy; Aceto, Nicola; Vincent-Jordan, Nicole; Szabolcs, Annamária; Chirn, Brian; Kreuzer, Johannes; Comaills, Valentine; Kalinich, Mark; Haas, Wilhelm; Ting, David T.; Toner, Mehmet; Vasudevan, Shobha; Haber, Daniel A.; Maheswaran, Shyamala; Micalizzi, Douglas S.

doi:10.1126/science.aay0939

Cited by 258 publications

(246 citation statements)

References 62 publications

Supporting

Mentioning

214

Contrasting

Order By: Relevance

“…They induce EMT through the transcriptional downregulation of E-cadherin (CDH1) while upregulation of mesenchymal-specific genes of Snail Family Transcriptional Repressor 1/2 (SNAI1/ SNA2), Zinc Finger E-Box Binding Homeobox 1/2 (ZEB1/2), Twist basic helix-loop-helix transcription factor 1/2 (TWIST1/2), Forkhead Box C1/2 (FOXC1/2), Transcription factor 3 (TCF3), Goosecoid Homeobox (GSC) [11]. Additional to these transcription factors, a substantial number of recent studies provided evidence in the involvement of other types of proteins including proto-oncogene Cellular Oncogene Fos (c-FOS), Zinc finger protein 367 (ZNF367), ribosomal protein RPL15, RNA-binding protein A-Kinase Anchor Protein (AKAP8) in regulation of breast cancer metastasis [12][13][14][15][16]. However, for understanding the cellular transition mechanisms lying in the heart of breast cancer metastasis, it is very important to shed light over the epigenetic mechanisms besides these regulations.…”

Section: Introductionmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

View full text Add to dashboard Cite

Thanks to the advancement in science and technology and a significant number of cancer research programs being carried out throughout the world, the prevention, prognosis and treatment of breast cancer are improving with a positive and steady pace. However, a stern thoughtful attention is required for the metastatic breast cancer casesthe deadliest of all types of breast cancer, with a character of relapse even when treated. In an effort to explore the less travelled avenues, we summarize here studies underlying the aspects of histone epigenetics in breast cancer metastasis. Authoritative reviews on breast cancer epigenetics are already available; however, there is an urgent need to focus on the epigenetics involved in metastatic character of this cancer. Here we put forward a comprehensive review on how different layers of histone epigenetics comprising of histone chaperones, histone variants and histone modifications interplay to create breast cancer metastasis landscape. Finally, we propose a hypothesis of integrating histone-epigenetic factors as biomarkers that encompass different breast cancer subtypes and hence could be exploited as a target of larger population.

show abstract

Section: Introductionmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

View full text Add to dashboard Cite

show abstract

“…S8). Overexpression of genes encoding ribosome protein components in CTCs has recently been shown to contribute to tumor metastasis (30).…”

Section: Reduced Ck Expression In Cancer Cells Is Often Associated Wimentioning

confidence: 99%

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Liu

Yan

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches, despite the aggressive nature of NSCLC. Here we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for detection of CTCs, with significantly improved detection rates and high specificity, in 33 NSCLC patients. Use of the HK2 marker identified underrepresented cytokeratin-negative (HK2 high /CK neg ) CTCs present in many blood samples but rarely detected in pleural effusions or cerebrospinal fluids of NSCLC patients.HK2 high /CK neg CTCs exhibited smaller sizes but consistent copy number variation profiles compared to CK pos CTCs. Surprisingly, CK expression levels were found to be independent of CTC epithelial-to-mesenchymal transition (EMT) status as measured by single-cell transcriptome profiling, challenging the long-standing association between CK expression and EMT. Our approach improves sensitivity of CTC detection in NSCLC and can potentially resolve a more complete spectrum of CTCs, regardless of their CK expression levels or epithelial traits.

show abstract

“…Ribosome biogenesis can increase the size of nucleolar organizing regions (NORs) which have long been used as a marker of tumor cell proliferation that negatively correlates with patient survival 39 . Richard Y. et al indicated that the increasing of ribosomal content in epithelial cell fates may enhance their metastatic potential in breast cancer 40 . Studies also demonstrated that drugs inhibiting ribosome biogenesis might provide a feasible therapeutic method for cancer treatment 41 .…”

Section: Dicussionmentioning

confidence: 99%

Integrative analysis of AGR2 based on data mining reveals new insights in breast cancer

Zhou¹,

Zhang²,

Liu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Belonging to the protein disulfide isomerase (PDI) family, anterior gradient 2 (AGR2) is overexpressed in mucus-secreting cells and endocrine organs such as breast, lung, and ovarian, but its exact function and regulation remain unclear. We aimed to perform integrative analysis of AGR2 in breast cancer.Methods: In our study, a serious of bioinformatic online databases were used to analyze the expression, regulation, prognostic value, and function of AGR2 in breast cancer.Results: The results suggested that AGR2 mRNA was overexpressed in non-basal-like or non-triple-negative breast cancer, but underexpressed in basal-like/ triple-negative breast cancer. AGR2 mRNA expression was correlated with its protein expression. Moreover, the expression of AGR2 was lower in more malignant breast cancer. Furthermore, we also found that DNA methylation, rather than copy number variation, led to AGR2 mRNA overexpression. Prognosis analysis showed no significant correlation between AGR2 level and survival, but in subtype investigation, patients with higher AGR2 level had a significantly better outcome in patients with basal-like / triple-negative breast cancer. Enrichment analysis for co-expression genes of AGR2 revealed that gene sets enriched for chromosome segregation, DNA conformation change, chromosomal region, and GABA receptor activity may play important roles in breast cancer, and that the most significant pathway was “ribosome biogenesis in eukaryotes”, in which negative co-expression genes of AGR2 were enriched.Conclusions: Overexpression of AGR2 was found in less malignant breast cancer, for the first time, our results propose that DNA methylation rather than copy number variation leads to AGR2 overexpression, which can predict favorable prognosis in basal-like/ triple-negative breast cancer, and AGR2 could be a possible regulator of ribosome biogenesis in patients with breast cancer.

show abstract

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

Cited by 258 publications

References 62 publications

A three layered histone epigenetics in breast cancer metastasis

A three layered histone epigenetics in breast cancer metastasis

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

Integrative analysis of AGR2 based on data mining reveals new insights in breast cancer

Contact Info

Product

Resources

About