Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Ohshima, Kenji; Morii, Eiichi

doi:10.3390/metabo11010028

Cited by 97 publications

(73 citation statements)

References 173 publications

(176 reference statements)

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“…Because pre-malignant and cancer cells must reprogram their metabolic state in every step of progression to survive in nutrient-altered conditions, metabolic reprogramming is recognized as a cancer hallmark [58]. Defining how cancer cells rewire metabolism towards proliferation, which our understanding of has progressed rapidly, opens new therapeutic intervention strategies [25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Cancers

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Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR’s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.

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Section: Discussionmentioning

confidence: 99%

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Cancers

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“…Recent studies have shown that mitophagy plays an important role in the metabolic transition of tumors and the maintenance of phenotype of cancer stem cells (CSCs). Continuous reprogramming of cellular metabolism is a critical milestone event in cancer ( Pavlova and Thompson, 2016 ; Chen et al, 2020 ; Ohshima and Morii, 2021 ). Metabolic alterations lead to enhanced uptake and utilization of glucose and amino acid nutrients from a nutrient-deficient environment and increased use of glycolysis/TCA cycle intermediates for macromolecular biosynthesis.…”

Section: The Role Of Mitophagy In Cancermentioning

confidence: 99%

The Nucleus/Mitochondria-Shuttling LncRNAs Function as New Epigenetic Regulators of Mitophagy in Cancer

Hoffman

et al. 2021

Front. Cell Dev. Biol.

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Mitophagy is a specialized autophagic pathway responsible for the selective removal of damaged or dysfunctional mitochondria by targeting them to the autophagosome in order to maintain mitochondria quality. The role of mitophagy in tumorigenesis has been conflicting, with the process both supporting tumor cell survival and promoting cell death. Cancer cells may utilize the mitophagy pathway to augment their metabolic requirements and resistance to cell death, thereby leading to increased cell proliferation and invasiveness. This review highlights major regulatory pathways of mitophagy involved in cancer. In particular, we summarize recent progress regarding how nuclear-encoded long non-coding RNAs (lncRNAs) function as novel epigenetic players in the mitochondria of cancer cells, affecting the malignant behavior of tumors by regulating mitophagy. Finally, we discuss the potential application of regulating mitophagy as a new target for cancer therapy.

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“…During tumor progression, tumor cells reprogramed their metabolic state from catabolism to anabolism for uncontrolled cell proliferation (15,16). Previous study reported that CDK7 inhibition suppresses human non-small-cell lung cancer cells through interference with cancer metabolism (25).…”

Section: Thz1 Disrupts the Cellular Metabolic Pathways Of B-all Cells In Vitromentioning

confidence: 99%

“…Metabolic reprogramming is a hallmark of tumor cells. The cellular metabolism of tumor cells is reprogrammed to fulfill the excessive metabolic demands for uncontrolled cell proliferation (15,16). Glycolysis, also known as the Warburg effect, is the initial step in glucose metabolism, which consumes a large number of glucose and results in lactate production even under adequate oxygen conditions.…”

Section: Introductionmentioning

confidence: 99%

CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism

Abudureheman

Xia

et al. 2021

Front. Oncol.

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B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL.

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Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Cited by 97 publications

References 173 publications

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

The Nucleus/Mitochondria-Shuttling LncRNAs Function as New Epigenetic Regulators of Mitophagy in Cancer

CDK7 Inhibitor THZ1 Induces the Cell Apoptosis of B-Cell Acute Lymphocytic Leukemia by Perturbing Cellular Metabolism

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