Angiopoietin-like 4 promotes glucose metabolism by regulating glucose transporter expression in colorectal cancer

Mizuno, Shodai; Seishima, Ryo; Yamasaki, Juntaro; Hattori, Kaoru; Ogiri, Masayo; Matsui, Shimpei; Shigeta, Kohei; Okabayashi, Koji; Nagano, Osamu; Li, Liang; Kitagawa, Yuko

doi:10.1007/s00432-022-03960-z

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…Of these genes, only ANGPTL4 was regulated (upregulated) in lines showing Dpep-inhibited glucose uptake/glycolysis and not in lines showing such inhibition. However, the literature indicates that ANGPLT4 activates glucose uptake [ 29 ] and either stimulates [ 30 ] or has no effect [ 31 ] on glycolysis.…”

Section: Resultsmentioning

confidence: 99%

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP

Zhou,

Nguyen,

Mun

et al. 2024

Cells

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We have designed cell-penetrating peptides that target the leucine zipper transcription factors ATF5, CEBPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. Though such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell context-dependent manner (in about two-thirds of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin-interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell context-dependent manner that in turn suppresses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

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Section: Resultsmentioning

confidence: 99%

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP

Zhou,

Nguyen,

Mun

et al. 2024

Cells

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“…Notably, ANGPTL4 also functions as a crucial metabolic regulator [ 55 ], implicated in genetic variations relating to a broad spectrum of blood lipids and metabolites. Furthermore, it plays a role in regulating the expression of glucose transport proteins, thereby promoting glucose metabolism within CRC [ 56 ]. The outcomes of cell communication analysis elucidate that SMCs in LM regulate the behavior of CRC cells, including CSCs, through the secretion of ANGPTL4.…”

Section: Discussionmentioning

confidence: 99%

Immune cell senescence and exhaustion promote the occurrence of liver metastasis in colorectal cancer by regulating epithelial-mesenchymal transformation

Lin,

Ma,

et al. 2024

Aging

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Background: Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunotherapy. However, there is currently a lack of comprehensive investigation into how senescent and exhausted immune cells contribute to LM. Methods: We gathered single-cell sequencing data from primary colorectal cancer (pCRC) and their corresponding matched LM tissues from 16 mCRC patients. In this study, we identified senescent and exhausted immune cells, performed enrichment analysis, cell communication, cell trajectory, and cell-based in vitro experiments to validate the results of single-cell multi-omics. This process allowed us to construct a regulatory network explaining the occurrence of LM. Finally, we utilized weighted gene co-expression network analysis (WGCNA) and 12 machine learning algorithms to create prognostic risk model. Results: We identified senescent-like myeloid cells (SMCs) and exhausted T cells (TEXs) as the primary senescent and exhausted immune cells. Our findings indicate that SMCs and TEXs can potentially activate transcription factors downstream via ANGPTL4-SDC1/SDC4, this activation plays a role in regulating the epithelial-mesenchymal transition (EMT) program and facilitates the development of LM, the results of cell-based in vitro experiments have provided confirmation of this conclusion. We also developed and validated a prognostic risk model composed of 12 machine learning algorithms. Conclusion: This study elucidates the potential molecular mechanisms underlying the occurrence of LM from various angles through single-cell multi-omics analysis in CRC. It also constructs a network illustrating the role of senescent or exhausted immune cells in regulating EMT.

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“…Ang-2 transcription augments the migration, invasion, and EMT of lung cancer cells [205]. While the role of Ang-4 (which acts as an agonist of the Tie-2 receptor) in tumor angiogenesis and invasion seems unclear, Ang-4 was recently shown to be associated with cancer progression by promoting glucose metabolism in colorectal cancer [206].…”

Section: Angiopoietins In Cancermentioning

confidence: 99%

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

Katsi

Papakonstantinou

Tsioufis

2023

IJMS

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The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice.

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Angiopoietin-like 4 promotes glucose metabolism by regulating glucose transporter expression in colorectal cancer

Cited by 7 publications

References 31 publications

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP

DPEP Inhibits Cancer Cell Glucose Uptake, Glycolysis and Survival by Upregulating Tumor Suppressor TXNIP

Immune cell senescence and exhaustion promote the occurrence of liver metastasis in colorectal cancer by regulating epithelial-mesenchymal transformation

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

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