The role of metabolic ecosystem in cancer progression — metabolic plasticity and mTOR hyperactivity in tumor tissues DOI Creative Commons
Anna Sebestyén, Titanilla Dankó, Dániel Sztankovics

et al.

Cancer and Metastasis Reviews, Journal Year: 2021, Volume and Issue: 40(4), P. 989 - 1033

Published: Dec. 1, 2021

Despite advancements in cancer management, tumor relapse and metastasis are associated with poor outcomes many cancers. Over the past decade, oncogene-driven carcinogenesis, dysregulated cellular signaling networks, dynamic changes tissue microenvironment, epithelial-mesenchymal transitions, protein expression within regulatory pathways, their part progression described several studies. However, complexity of metabolic enzyme is considerably under evaluated. Alterations metabolism determine individual phenotype behavior cells, which a well-recognized hallmark progression, especially adaptation mechanisms underlying therapy resistance. In symbiosis, cells compete, communicate, even feed each other, supervised by cells. Metabolic reprogramming forms unique fingerprint for tissue, depending on content genetic, epigenetic, microenvironmental alterations developing cancer. Based its sensing effector functions, mechanistic target rapamycin (mTOR) kinase considered master regulator adaptation. Moreover, mTOR hyperactivity prognosis various types. situ phenotyping recent studies highlights importance plasticity, hyperactivity, role progression. this review, we update developments ecosystem, plasticity could provide new research directions biology. addition, suggest pathomorphological analytical relating to alterations, activity, associations necessary improve understanding heterogeneity expand therapeutic management

Language: Английский

3D microtumors in vitro supported by perfused vascular networks DOI Creative Commons

Agua Sobrino,

Duc T. T. Phan, Rupsa Datta

et al.

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: Aug. 23, 2016

Abstract There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs vitro . This “organs-on-chips” approach aims capture key structural physiological characteristics of the target tissue. Here we describe vascularized microtumors (VMTs). “tumor-on-a-chip” platform incorporates tumor stromal cells grow 3D extracellular matrix depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal breast cancer vigorously respond standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms action also distinguished, find drugs targeting only VEGFRs (Apatinib Vandetanib) are not effective, whereas VEGFRs, PDGFR Tie2 (Linifanib Cabozantinib) do regress vasculature. Tumors VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared their surrounding stroma, many higher free/bound ratio consistent known preference aerobic glycolysis. The provides unique studying solid tumors

Language: Английский

Citations

343
Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment DOI Creative Commons
Go J. Yoshida

Journal of Hematology & Oncology, Journal Year: 2017, Volume and Issue: 10(1)

Published: March 9, 2017

The 2016 Nobel Prize in Physiology or Medicine was awarded to the researcher that discovered autophagy, which is an evolutionally conserved catabolic process degrades cytoplasmic constituents and organelles lysosome. Autophagy plays a crucial role both normal tissue homeostasis tumor development necessary for cancer cells adapt efficiently unfavorable microenvironment characterized by hypo-nutrient conditions. This protein degradation leads amino acid recycling, provides sufficient substrates cellular survival proliferation. constitutively activated due deregulation of PI3K/Akt/mTOR signaling pathway, enables them exhibit robust proliferation at pre-metastatic niche. That why just activation autophagy with mTOR inhibitor often fails vain. In contrast, disturbance autophagy–lysosome flux endoplasmic reticulum (ER) stress unfolded response (UPR), finally increased apoptotic cell death tissue. Accumulating evidence suggests has close relationship programmed death, while uncontrolled itself induces autophagic cells. Autophagic originally defined as accompanied large-scale vacuolization cytoplasm. However, "double-edged sword" it can either promote suppress microenvironment. Furthermore, several studies drug re-positioning suggest "conventional" agents used treat diseases other than have antitumor therapeutic effects activating/suppressing autophagy. Because ever increasing failure rates high cost associated anticancer development, this strategy attracted attention because safety profiles these medicines are well known. Antimalarial such artemisinin disease-modifying antirheumatic (DMARD) typical examples affect regulation use. review article focuses on recent advances some novel strategies target view treating/preventing malignant neoplasms.

Language: Английский

Citations

213
Optical imaging of metabolic dynamics in animals DOI Creative Commons
Lingyan Shi, Chaogu Zheng, Yihui Shen

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: July 25, 2018

Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing stimulated Raman scattering (DO-SRS) microscopy image situ activities. Enzymatic incorporation D2O-derived into macromolecules generates carbon-deuterium (C-D) bonds, which track biosynthesis tissues can be imaged by SRS situ. Within the broad vibrational spectra C-D discover lipid-, protein-, DNA-specific shifts develop spectral unmixing methods obtain signals macromolecular selectivity. DO-SRS enables us probe de novo lipogenesis animals, protein without tissue bias, simultaneously visualize lipid metabolism reveal their different dynamics. microscopy, being noninvasive, universally applicable, cost-effective, adapted range systems study development, homeostasis, aging, tumor heterogeneity.

Language: Английский

Citations

212
Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis DOI Creative Commons
Kenji Ohshima, Eiichi Morii

Metabolites, Journal Year: 2021, Volume and Issue: 11(1), P. 28 - 28

Published: Jan. 2, 2021

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of primary site, intravasation into vessels where anchorage-independent is required, colonization distant organs environment distinct from that site. Thus, cancer must reprogram their state every step progression. Metabolic reprogramming now recognized as a hallmark supports growth. Elucidating underlying mechanisms may help identifying targets treatment strategies. This review summarizes our current understanding progression metastasis, cell adaptation to microenvironment, defense against oxidative stress vessels, metastasis.

Language: Английский

Citations

156
Linking metabolic reprogramming to therapy resistance in cancer DOI
Andrea Morandi, Stefano Indraccolo

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2017, Volume and Issue: 1868(1), P. 1 - 6

Published: Jan. 6, 2017

Language: Английский

Citations

144
Applications of vibrational tags in biological imaging by Raman microscopy DOI
Zhilun Zhao, Yihui Shen, Fanghao Hu

et al.

The Analyst, Journal Year: 2017, Volume and Issue: 142(21), P. 4018 - 4029

Published: Jan. 1, 2017

In this article, we review the recent successful applications of SRS and vibrational tags for solving biological problems.

Language: Английский

Citations

93
Recent advances in heat shock proteins in cancer diagnosis, prognosis, metabolism and treatment DOI Open Access
Shuxian Yang,

Haiyan Xiao,

Li Cao

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 142, P. 112074 - 112074

Published: Aug. 20, 2021

Heat shock proteins (HSPs) are a group of proteins, also known as molecular chaperones, which participate in protein folding and maturation response to stresses or high temperature. According their weights, mammalian HSPs classified into HSP27, HSP40, HSP60, HSP70, HSP90, large HSPs. Previous studies have revealed that play important roles oncogenesis malignant progression because they can modulate all six hallmark traits cancer. Because this, been propelled the spotlight biomarkers for cancer diagnosis prognosis, well an exciting anticancer drug target. However, relationship between expression level activity diagnosis, metabolism treatment is not clear has completely established. Herein, this review summarizes discusses recent advances perspectives major regulators therapeutic targets therapy, may provide new directions improve accuracy develop more effective safer therapeutics.

Language: Английский

Citations

79
Immune cell metabolism and metabolic reprogramming DOI Open Access
Chenchen Hu,

Yuxin Xuan,

Xiyang Zhang

et al.

Molecular Biology Reports, Journal Year: 2022, Volume and Issue: 49(10), P. 9783 - 9795

Published: June 13, 2022

Language: Английский

Citations

66
TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor DOI Open Access
Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio

et al.

Genes, Journal Year: 2018, Volume and Issue: 9(4), P. 195 - 195

Published: April 5, 2018

Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) a molecular chaperone involved the regulation of energetic metabolism cancer cells. This protein highly expressed several cancers, such as glioblastoma, colon, breast, prostate lung cancers often associated with drug resistance. However, TRAP1 also downregulated specific tumors, ovarian, bladder renal where its lower expression worst prognoses chemoresistance. only mitochondrial member Heat Shock 90 (HSP90) family that directly interacts respiratory complexes, contributing their stability activity but it still unclear if interactions lead reduced or increased capacity. The role enhance suppress oxidative phosphorylation; effects on development progression are controversial. These observations encourage study mechanisms responsible for dualist oncogene oncosuppressor types. In this review, puzzling functions were recapitulated special focus correlation between We wanted investigate whether metabolism-targeting drugs can efficiently interfere they might be combined chemotherapeutics molecular-targeted agents counteract resistance reduce therapeutic failure.

Language: Английский

Citations

80
High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity DOI
Pengfei Hai, Toru Imai,

Song Xu

et al.

Nature Biomedical Engineering, Journal Year: 2019, Volume and Issue: 3(5), P. 381 - 391

Published: April 1, 2019

Language: Английский

Citations

73