Why All the Fuss about Oxidative Phosphorylation (OXPHOS)? DOI
Yibin Xu, Ding Xue,

Armand Bankhead

et al.

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(23), P. 14276 - 14307

Published: Oct. 26, 2020

Certain subtypes of cancer cells require oxidative phosphorylation (OXPHOS) to survive. Increased OXPHOS dependency is frequently a hallmark stem and resistant chemotherapy targeted therapies. Suppressing the function might also influence tumor microenvironment by alleviating hypoxia improving antitumor immune response. Thus, targeting promising strategy treat various cancers. A growing arsenal therapeutic agents under development inhibit this biological process. This Perspective provides an overview structure complexes, their functions in cancer, relevant research tools models, as well limitations drug targets. We focus on current status inhibitors potential strategies strengthen clinical applications.

Language: Английский

The metabolism of cancer cells during metastasis DOI
Gabriele Bergers, Sarah‐Maria Fendt

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(3), P. 162 - 180

Published: Jan. 18, 2021

Language: Английский

Citations

669

Applications of single-cell sequencing in cancer research: progress and perspectives DOI Creative Commons

Yalan Lei,

Rong Tang, Jin Xu

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: June 9, 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics is a powerful tool to decipher the cellular molecular landscape at single-cell resolution, unlike bulk which provides averaged data. The use of sequencing in cancer research has revolutionized our understanding biological characteristics dynamics within lesions. In this review, we summarize emerging technologies recent progress obtained by information related landscapes malignant cells immune cells, tumor heterogeneity, circulating underlying mechanisms behaviors. Overall, prospects facilitating diagnosis, targeted therapy prognostic prediction among spectrum tumors are bright. near future, advances will undoubtedly improve highlight potential precise therapeutic targets for patients.

Language: Английский

Citations

356

Single‐cell RNA sequencing in cancer research DOI Creative Commons
Yijie Zhang, Dan Wang, Peng Miao

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: March 1, 2021

Abstract Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well new cell-specific markers cell types. scRNA-seq plays an important role various aspects tumor research. It reveals the heterogeneity cells monitors progress development, thereby preventing further cellular deterioration. Furthermore, transcriptome analysis immune tissue be used to classify cells, their escape mechanisms drug resistance mechanisms, develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables study intercellular communication interaction non-malignant reveal carcinogenesis. provides technical means for development research is expected make significant breakthroughs field. This review focuses on principles scRNA-seq, emphasis application heterogeneity, pathogenesis, treatment.

Language: Английский

Citations

254

Insights Gained from Single-Cell Analysis of Immune Cells in the Tumor Microenvironment DOI
Xianwen Ren, Lei Zhang, Yuanyuan Zhang

et al.

Annual Review of Immunology, Journal Year: 2021, Volume and Issue: 39(1), P. 583 - 609

Published: Feb. 27, 2021

Understanding tumor immune microenvironments is critical for identifying modifiers of cancer progression and developing immunotherapies. Recent applications single-cell RNA sequencing (scRNA-seq) in dissecting have brought important insights into the biology tumor-infiltrating cells, including their heterogeneity, dynamics, potential roles both disease response to checkpoint inhibitors other This review focuses on advances knowledge acquired from scRNA-seq studies across multiple types human tumors, with a particular emphasis study phenotypic plasticity lineage dynamics cells environment. We also discuss several imminent questions emerging observations solutions horizon.

Language: Английский

Citations

250

Metastasis-Initiating Cells and Ecosystems DOI Open Access
Joan Massagué, Karuna Ganesh

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 971 - 994

Published: April 1, 2021

Abstract Metastasis is initiated and sustained through therapy by cancer cells with stem-like immune-evasive properties, termed metastasis-initiating (MIC). Recent progress suggests that MICs result from the adoption of a normal regenerative progenitor phenotype malignant cells, intrinsic programs to survive stresses metastatic process, undergo epithelial–mesenchymal transitions, enter slow-cycling states for dormancy, evade immune surveillance, establish supportive interactions organ-specific niches, co-opt systemic factors growth recurrence after therapy. Mechanistic understanding molecular mediators MIC phenotypes host tissue ecosystems could yield therapeutics improve patient outcomes. Significance: Understanding origins, traits, vulnerabilities capacity initiate metastasis in distant organs, microenvironments support ability these surveillance regenerate tumor, critical developing strategies prevention treatment advanced cancer. Leveraging recent our here we review nature their offer perspective on how this knowledge informing innovative treatments cancers.

Language: Английский

Citations

246

Mechanoresponsive metabolism in cancer cell migration and metastasis DOI Creative Commons
Matthew R. Zanotelli, Jian Zhang, Cynthia A. Reinhart‐King

et al.

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(7), P. 1307 - 1321

Published: April 28, 2021

Language: Английский

Citations

219

Steps in metastasis: an updated review DOI
Jamal Majidpoor, Keywan Mortezaee

Medical Oncology, Journal Year: 2021, Volume and Issue: 38(1)

Published: Jan. 1, 2021

Language: Английский

Citations

213

Mitochondrial RNA modifications shape metabolic plasticity in metastasis DOI Creative Commons
Sylvain Delaunay, Gloria Pascual, Bohai Feng

et al.

Nature, Journal Year: 2022, Volume and Issue: 607(7919), P. 593 - 603

Published: June 29, 2022

Aggressive and metastatic cancers show enhanced metabolic plasticity1, but the precise underlying mechanisms of this remain unclear. Here we how two NOP2/Sun RNA methyltransferase 3 (NSUN3)-dependent modifications-5-methylcytosine (m5C) its derivative 5-formylcytosine (f5C) (refs.2-4)-drive translation mitochondrial mRNA to power metastasis. Translation mitochondrially encoded subunits oxidative phosphorylation complex depends on formation m5C at position 34 in tRNAMet. m5C-deficient human oral cancer cells exhibit increased levels glycolysis changes their function that do not affect cell viability or primary tumour growth vivo; however, plasticity is severely impaired as tumours metastasize efficiently. We discovered CD36-dependent non-dividing, metastasis-initiating require activate invasion dissemination. Moreover, a mitochondria-driven gene signature patients with head neck predictive for metastasis disease progression. Finally, confirm switch allows can be pharmacologically targeted through inhibition vivo. Together, our results reveal site-specific modifications could therapeutic targets combat

Language: Английский

Citations

198

Single‐cell RNA sequencing in breast cancer: Understanding tumor heterogeneity and paving roads to individualized therapy DOI Creative Commons
Shuning Ding, Xiaosong Chen, Kunwei Shen

et al.

Cancer Communications, Journal Year: 2020, Volume and Issue: 40(8), P. 329 - 344

Published: July 12, 2020

Abstract Single‐cell RNA sequencing (scRNA‐seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA‐seq sensitivity, accuracy, and efficiency have improved due to innovations including more sensitive, automated, cost‐effective single‐cell isolation methods with higher throughput as well ongoing technological development protocols. Among variety current approaches distinct features, researchers can choose most suitable method carry out their research. By profiling single cells in complex population mix, presents great advantages over traditional dissecting heterogeneity cell populations hidden bulk analysis exploring rare types associated tumorigenesis metastasis. studies recent years field breast cancer research clustered different molecular subtypes identify may correlate poor prognosis drug resistance. The has also been used explain tumor microenvironment by identifying immune subsets be immunosurveillance are potential immunotherapy targets. Moreover, diverse applications besides heterogeneity, cell‐cell communications, regulatory states, distributions, more. promising tool facilitate individualized therapy its ability define treatment Although therapeutic selection currently limited, application this prospective. Joint efforts original ideas needed better implement technologies pave way for management. This review provides brief introduction on available along corresponding strengths weaknesses act reference We discuss analysis, therapy, other directions mentioned above reviewing published studies. Finally, we limitations technical problems remain overcome.

Language: Английский

Citations

188

The Single‐Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer DOI Creative Commons
Yutian Zou, Feng Ye, Yanan Kong

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 10(5)

Published: Dec. 18, 2022

Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain have an extremely poor prognosis and low response rates to anti-PD-1/L1 immune checkpoint therapy compared those at other sites. Therefore, it is urgent investigate underlying mechanism resistance develop more effective immunotherapy strategies these patients. Using single-cell RNA sequencing, a high-resolution map entire tumor ecosystem based on 44 473 cells from cancer metastases depicted. Identified by canonical markers confirmed multiplex immunofluorescent staining, metastatic features remarkable reprogramming immunosuppressive such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic CCL18+ M2-like macrophages, RGS5+ cancer-associated fibroblasts, LGALS1+ microglial cells. In addition, PD-1 PD-L1/2 are barely expressed in CD8+ cancer/immune/stromal respectively. Interactions molecules LAG3-LGALS3 TIGIT-NECTIN2 between found play dominant roles escape. summary, this study dissects intratumoral heterogeneity microenvironment first time, providing insights into most appropriate

Language: Английский

Citations

172