The Role of Cholesterol Metabolism and Its Regulation in Tumor Development DOI Creative Commons

Yongmei Wu,

Wenqian Song,

Su Min

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(7)

Published: March 27, 2025

ABSTRACT Background Within the tumor microenvironment, cells undergo metabolic reprogramming of cholesterol due to intrinsic cellular alterations and changes in extracellular milieu. Furthermore, within this microenvironment influences immune landscape tumors, facilitating evasion consequently promoting tumorigenesis. These biological involve modifications numerous enzymes associated with uptake synthesis, including NPC1L1, SREBP, HMGCR, SQLE, PCSK9. Review This review systematically summarizes role metabolism its cancer progression, examines mechanisms through which dysregulation affects discusses recent advancements therapies that target metabolism. Conclusion Targeting metabolism‐related can inhibit growth, reshape landscapes, rejuvenate antitumor immunity, offering potential therapeutic avenues treatment.

Language: Английский

Targeting mTOR for cancer therapy DOI Creative Commons
Hui Hua,

Qingbin Kong,

Hongying Zhang

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: July 5, 2019

Mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity. mTOR usually assembled into several complexes such as complex 1/2 (mTORC1/2). In cooperation with raptor, rictor, LST8, mSin1, key components in mTORC1 or mTORC2, catalyzes the phosphorylation multiple targets ribosomal S6 β-1 (S6K1), eukaryotic translation initiation factor 4E binding 1 (4E-BP1), Akt, C (PKC), type-I insulin-like growth receptor (IGF-IR), thereby synthesis, nutrients signaling, migration. Activation promotes tumor metastasis. Many inhibitors have been developed to treat cancer. While some approved human cancer, more are being evaluated clinical trials. Here, we update recent advances exploring signaling development for cancer therapy. addition, discuss mechanisms underlying resistance cells.

Language: Английский

Citations

785
Regulation and metabolic functions of mTORC1 and mTORC2 DOI

Angelia Szwed,

Eugene Kim, Estela Jacinto

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(3), P. 1371 - 1426

Published: Feb. 18, 2021

Cells metabolize nutrients for biosynthetic and bioenergetic needs to fuel growth proliferation. The uptake of from the environment their intracellular metabolism is a highly controlled process that involves cross talk between signaling metabolic pathways. Despite constant fluctuations in nutrient availability environmental signals, normal cells restore homeostasis maintain cellular functions prevent disease. A central molecule integrates with mechanistic target rapamycin (mTOR). mTOR protein kinase responds levels signals. forms two complexes, mTORC1, which sensitive rapamycin, mTORC2, not directly inhibited by this drug. Rapamycin has facilitated discovery various mTORC1 metabolism. Genetic models disrupt either or mTORC2 have expanded our knowledge cellular, tissue, as well systemic Nevertheless, regulation particularly metabolism, lagged behind. Since an important cancer, aging, other metabolism-related pathologies, understanding distinct overlapping complexes vital development more effective therapeutic strategies. This review discusses key discoveries recent findings on complexes. We highlight cancer but also discuss examples mTOR-mediated reprogramming occurring stem immune cells, type 2 diabetes/obesity, neurodegenerative disorders, aging.

Language: Английский

Citations

493
β-Hydroxybutyrate suppresses colorectal cancer DOI

Oxana Dmitrieva-Posocco,

Andrea C. Wong, Patrick Lundgren

et al.

Nature, Journal Year: 2022, Volume and Issue: 605(7908), P. 160 - 165

Published: April 27, 2022

Language: Английский

Citations

210
Metabolic communication in the tumour–immune microenvironment DOI
Kung‐Chi Kao,

Stefania Vilbois,

Chin‐Hsien Tsai

et al.

Nature Cell Biology, Journal Year: 2022, Volume and Issue: 24(11), P. 1574 - 1583

Published: Oct. 13, 2022

Language: Английский

Citations

191
Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications DOI Creative Commons
Xinyang Zhong, Xuefeng He, Yaxian Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 1, 2022

Colorectal cancer (CRC) is the third most common and second leading cause of cancer-related death worldwide. Countless CRC patients undergo disease progression. As a hallmark cancer, Warburg effect promotes metastasis remodels tumor microenvironment, including promoting angiogenesis, immune suppression, cancer-associated fibroblasts formation drug resistance. Targeting metabolism would be promising method for treatment CRC. In this review, we summarize information about roles in microenvironment to elucidate mechanisms governing identify novel targets therapy.

Language: Английский

Citations

160
Inflammation: the incubator of the tumor microenvironment DOI
Dominic Denk, Florian R. Greten

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(11), P. 901 - 914

Published: July 28, 2022

Language: Английский

Citations

155
Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy DOI Open Access
Miljana Nenkov, Yunxia Ma,

Nikolaus Gaßler

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6262 - 6262

Published: June 10, 2021

Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and leading causes cancer-related death worldwide. Metabolic reprogramming, a hallmark cancer, closely related to initiation progression carcinomas, including CRC. Accumulating evidence shows that activation oncogenic pathways loss tumor suppressor genes regulate metabolic reprogramming mainly involved in glycolysis, glutaminolysis, one-carbon metabolism lipid metabolism. The abnormal program provides cells with abundant energy, nutrients redox requirements support their malignant growth metastasis, which accompanied by impaired flexibility microenvironment (TME) dysbiosis gut microbiota. crosstalk between cells, components TME intestinal microbiota further facilitates CRC cell proliferation, invasion metastasis leads therapy resistance. Hence, target dysregulated metabolism, microbiota, novel preventive therapeutic applications are required. In this review, dysregulation programs, molecular pathways, addressed. Possible strategies, inhibition immune CRC, as well modulation aberrant discussed.

Language: Английский

Citations

108
Metabolism and Colorectal Cancer DOI Creative Commons
Joseph C. Sedlak, Ömer Yılmaz, Jatin Roper

et al.

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2022, Volume and Issue: 18(1), P. 467 - 492

Published: Nov. 2, 2022

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal cellular waste in nutrient-poor environments. Intestinal stem (ISCs), primary cell origin for CRCs, must adapt their along adenoma-carcinoma sequence to unique features complex microenvironment that include interactions with intestinal epithelial cells, immune stromal commensal microbes, dietary components. Emerging evidence implicates modifiable risk factors related environment, such as diet, important pathogenesis. Here, we focus on describing ISCs, diets influence initiation, genetics metabolism, tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, enhancing or supporting tumorigenesis becoming better understood. Thus, greater knowledge holds promise improved prevention treatment.

Language: Английский

Citations

101
Nuclear genome-derived circular RNA circPUM1 localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma DOI Creative Commons

Wei Gong,

Jiancheng Xu, Yan Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 14, 2022

Abstract Circular RNAs (circRNAs) were shown to play an important role in the occurrence and progression of tumors. However, functions nuclear genome-derived circRNAs localized mitochondria tumor cells remain largely elusive. Here, we report that circPUM1, a circular RNA derived from back-splicing pre-mRNAs genome PUM1, localizes mitochondria. The expression level circPUM1 is positively correlated with HIF1α accumulation under CoCl 2 -induced intracellular hypoxic-like condition esophageal squamous cell carcinoma (ESCC) lines. Importantly, acts as scaffold for interaction between UQCRC1 UQCRC2 ESCC Knock-down would result lower oxygen concentration, downregulated oxidative phosphorylation, decrease mitochondrial membrane potential, increase ROS generation shrinking mitochondria, respectively. CircPUM1 depletion induces dysfunction complex III cleavage caspase3 spontaneously. Interestingly, disruption led pyroptosis initiates death Therefore, conclude plays critical maintaining stability enhance phosphorylation ATP production moreover propose exploit during adaptation.

Language: Английский

Citations

83
Hypoxia signaling in cancer: Implications for therapeutic interventions DOI Creative Commons
Yan Zhuang,

Kua Liu,

Qinyu He

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(1)

Published: Jan. 23, 2023

Abstract Hypoxia is a persistent physiological feature of many different solid tumors and key driver malignancy, in recent years, it has been recognized as an important target for cancer therapy. occurs the majority due to poor vascular oxygen supply that not sufficient meet needs rapidly proliferating cells. A hypoxic tumor microenvironment (TME) can reduce effectiveness other therapies, such radiotherapy, chemotherapy, immunotherapy. In this review, we discuss critical role hypoxia development, including metabolism, immunity, angiogenesis. The treatment methods TME are summarized, hypoxia‐targeted therapy improving oxygenation by alleviating itself. Hyperoxia be used improve tissue partial pressure relieve hypoxia. We focus on underlying mechanisms hyperoxia their impact current therapies prospects treatment.

Language: Английский

Citations

63