The NALCN channel regulates metastasis and nonmalignant cell dissemination DOI Creative Commons
Eric P. Rahrmann, David Shorthouse,

Amir Jassim

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(12), P. 1827 - 1838

Published: Sept. 29, 2022

Abstract We identify the sodium leak channel non-selective protein (NALCN) as a key regulator of cancer metastasis and nonmalignant cell dissemination. Among 10,022 human cancers, NALCN loss-of-function mutations were enriched in gastric colorectal cancers. Deletion Nalcn from gastric, intestinal or pancreatic adenocarcinomas mice did not alter tumor incidence, but markedly increased number circulating cells (CTCs) metastases. Treatment these with gadolinium—a blocker—similarly CTCs that lacked oncogenic never developed caused shedding epithelial into blood at levels equivalent to those seen tumor-bearing animals. These trafficked distant organs form normal structures including lung epithelium, kidney glomeruli tubules. Thus, regulates solid tissues independent cancer, divorcing this process tumorigenesis unmasking potential new target for antimetastatic therapies.

Language: Английский

Liquid biopsy enters the clinic — implementation issues and future challenges DOI
Michail Ignatiadis, George W. Sledge, Stefanie S. Jeffrey

et al.

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 18(5), P. 297 - 312

Published: Jan. 20, 2021

Language: Английский

Citations

864

High-content CRISPR screening DOI Open Access
Christoph Bock, Paul Datlinger, Florence M. Chardon

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Feb. 10, 2022

Language: Английский

Citations

371

Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy DOI Creative Commons
Jian Kang, Natalie Brajanovski, Keefe T. Chan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 30, 2021

Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth proliferation. The ribosomal proteins (RPs), comprising the structural parts of ribosome, essential ribosome assembly function. In addition to their canonical functions, multiple RPs have extra-ribosomal functions including activation p53-dependent or p53-independent pathways in response stress, resulting cycle arrest apoptosis. Defects biogenesis, translation, individual RPs, mutations been linked a diverse range human congenital disorders termed ribosomopathies. Ribosomopathies characterized by tissue-specific phenotypic abnormalities higher cancer risk later life. Recent discoveries somatic tumor types reinforce connections between defects cancer. this article, we review most recent advances understanding molecular consequences RP ribosomopathies We particularly discuss basis transition from hypo- hyper-proliferation with elevated risk, paradox "Dameshek's riddle." Furthermore, current treatments prospective therapies targeting defects. also highlight stress-based therapeutics. Importantly, insights into mechanisms resistance bring new perspectives susceptibility clinical implications therapy.

Language: Английский

Citations

258

N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression DOI Creative Commons
Zihao Dai, Hai‐Ning Liu, Junbin Liao

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(16), P. 3339 - 3355.e8

Published: Aug. 1, 2021

Language: Английский

Citations

217

High-content CRISPR screening DOI
Christoph Bock, Paul Datlinger, Florence M. Chardon

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Feb. 10, 2022

Language: Английский

Citations

204

Liquid biopsies: Potential and challenges DOI Creative Commons

Isabel Heidrich,

Lucija Ačkar,

Parinaz Mossahebi Mohammadi

et al.

International Journal of Cancer, Journal Year: 2020, Volume and Issue: 148(3), P. 528 - 545

Published: July 19, 2020

The analysis of tumor cells or cell products obtained from blood other body fluids ("liquid biopsy" [LB]) provides a broad range opportunities in the field oncology. Clinical application areas include early detection cancer recurrence, individual risk assessment and therapy monitoring. LB allows to portray entire disease as are released all metastatic primary sites, providing comprehensive real-time information on evolution, therapeutic targets mechanisms resistance therapy. Here, we focus most prominent markers, circulating (CTCs) tumor-derived DNA (ctDNA), patients with breast, prostate, lung colorectal cancer, four frequent types Europe. After brief introduction key technologies used detect CTCs ctDNA, discuss recent clinical studies these biomarkers for prognostication well prediction monitoring therapies. We also point out current methodological biological limitations that still hamper implementation into practice.

Language: Английский

Citations

202

Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance DOI Creative Commons
Amr Elhamamsy, Brandon J. Metge, Heba Allah Alsheikh

et al.

Cancer Research, Journal Year: 2022, Volume and Issue: 82(13), P. 2344 - 2353

Published: March 18, 2022

Abstract Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is multistep process begins in the nucleolus concludes cytoplasm. The tightly controlled by multiple checkpoint surveillance pathways. Perturbations these checkpoints pathways can lead to hyperactivation ribosome biogenesis. Emerging evidence suggests cancer cells harbor specialized class ribosomes (onco-ribosomes) facilitates oncogenic program, modulates cellular functions, promotes metabolic rewiring. Mutations proteins, processing, assembly factors result ribosomopathies associated with an increased risk developing malignancies. Recent studies have linked mutations aberrant poor prognosis, highlighting ribosome-targeted therapy promising approach for treating patients cancer. Here, we summarize various aspects dysregulation impact resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, clinical outcome. target, understanding important determinants this will allow improved perhaps selective strategies target biosynthesis.

Language: Английский

Citations

178

Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins DOI Open Access

Annalisa Pecoraro,

Martina Pagano,

Giulia Russo

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5496 - 5496

Published: May 23, 2021

Cytosolic ribosomes (cytoribosomes) are macromolecular ribonucleoprotein complexes that assembled from ribosomal RNA and proteins, which essential for protein biosynthesis. Mitochondrial (mitoribosomes) perform translation of the proteins oxidative phosphorylation system. The biogenesis cytoribosomes mitoribosomes includes processing, modification binding to is assisted by numerous factors. This a major energy-consuming process in cell and, therefore, highly coordinated sensitive several cellular stressors. In mitochondria, regulation mitoribosome respiration, linked growth proliferation. review briefly overviews key stages cytosolic mitochondrial ribosome biogenesis; summarizes main steps alterations occurring during tumorigenesis, highlighting changes expression level (CRPs) (MRPs) different types tumors; focuses on currently available information regarding extra-ribosomal functions CRPs MRPs correlated cancer; discusses role as biomarkers and/or molecular targets cancer treatment.

Language: Английский

Citations

128

STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma DOI
Jing Hu, Francisco J. Sánchez‐Rivera, Zhenghan Wang

et al.

Nature, Journal Year: 2023, Volume and Issue: 616(7958), P. 806 - 813

Published: March 29, 2023

Language: Английский

Citations

124

Translational control of stem cell function DOI
James A. Saba, Kifayathullah Liakath‐Ali, Rachel Green

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(10), P. 671 - 690

Published: July 16, 2021

Language: Английский

Citations

120