Table 2 List of literature on metabolic types and tumor metastasis

Glycolysis

RFX6

RFX6 facilitated aerobic glycolysis-mediated growth and metastasis of HCC through targeting PGAM1.

¹⁷⁸

-

Using single-cell RNA sequencing and spatial transcriptomics, a shift from glycolysis to oxidative phosphorylation in a cluster of disseminated cancer cells in breast cancer patients was discovered, highlighting the metabolic evolution critical for early metastasis.

¹⁷⁹

circRPN2

CircRPN2 Inhibited aerobic glycolysis and metastasis in HCC.

¹⁸⁰

NEAT1

NEAT1 regulated glycolysis through isoform switching, playing a crucial isoform-specific role in breast cancer metastasis independently of paraspeckles.

³³

ZEB1

ZEB1, a transcription factor, intensified the Warburg effect in HCC, and ZEB1 does this by activating PFKM, a crucial glycolytic enzyme, thus promoting both tumor growth and metastasis in HCC.

¹⁸¹

CD47

High CD47 expression in CRC correlated with worse prognosis and facilitated cancer growth and metastasis by increasing aerobic glycolysis and activating ERK signaling through the stabilization of ENO1.

¹⁸²

NK cells

Peripheral blood NK cells from patients with metastatic breast cancer exhibited decreased interferon-γ production, reduced cytotoxicity, and metabolic impairments including lower glycolysis and oxidative phosphorylation, and also displayed significant mitochondrial fragmentation.

¹⁴⁴

macrophages

Tumor-derived exosomes (TDEs) caused macrophages to shift their metabolism towards glycolysis, resulting in increased lactate production. This shift enhances PD-L1 expression via an NF-kB-dependent pathway, promoting an immunosuppressive environment that aids tumor metastasis, specifically in lung cancer.

¹⁸³

macrophages

Exposure to carbon black ultrafine particles shifted lung macrophage metabolism towards glycolysis, increases lactate production, and activates the HIF1α axis, thus leading to mitochondrial damage and reduced respiration and increasing lung cancer incidence and metastasis.

¹⁸⁴

TAMs

Increased glucose uptake by M2-like TAMs enhanced the hexosamine biosynthetic pathway, leading to the O-GlcNAcylation of lysosomal Cathepsin B, which promotes cancer metastasis and chemoresistance.

¹⁸⁵

FA-EDTA/ICG-Lip NPs

A nanoplatform called FA-EDTA/ICG-Lip NPs targeted breast cancer by inhibiting glycolysis and leveraging acidic environments to enhance immune attacks, thus impeding tumor growth and metastasis.

¹⁸⁶

BLG@TPGS NPs

Nanoparticles (BLG@TPGS NPs) targeted and disrupted energy production in TNBC cells by inhibiting mitochondrial functions, including glycolysis, effectively halting tumor growth and spread through a combined chemo-co-starvation therapy approach with reduced toxicity.

¹⁸⁷

Nano-activator

A nano-activator that targets and modifies PKM2, triggered by a tumor-related enzyme, formed nanofibers that promote the formation of active PKM2 groups, effectively disrupting the energy supply necessary for tumor growth.

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DMNPN

The nanoregulator DMNPN inhibited tumor glycolysis and glutaminase, reducing glucose and glutamine uptake by cancer cells and enhancing nutrient availability for T cells, thereby stalling tumor growth and boosting T cell immune efficacy.

¹⁸⁹

Lipid metabolism

FASN

In male breast cancer, activation of fatty acid metabolism, specifically through the FASN enzyme, was associated with enhanced metastasis of cancer cells and reduced immune cell infiltration.

¹⁹⁰

FASN

In cervical cancer, FASN reprogrammed cholesterol metabolism and activates the c-Src/AKT/FAK signaling pathway associated with lipid rafts, resulting in increased cell migration and invasion.

¹⁹¹

FABP5

FABP5 facilitated the reprogramming of fatty acid metabolism, and this metabolic reprogramming leads to an increase in intracellular fatty acid that activate NF-κB signaling, inducing lymph node metastasis in cervical cancer.

¹⁹²

PTPRO

PTPRO repressed CRC tumorigenesis and progression by activating the AKT/mTOR signaling pathway and reprogramming fatty acid metabolism.

¹⁹³

HKDC1

HKDC1 reprogrammed lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex.

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ACSL4

ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway and promotes tumor metastasis.

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macrophages

Exosomes released from PD-L1(+) tumor associated macrophages promote peritoneal metastasis of epithelial ovarian cancer by up-regulating T cell lipid metabolism thus leading to reactive oxygen species accumulation.

¹⁹⁶

macrophages

Macrophages with upregulated CD36 expression were enriched their lipid droplets by engulfing tumor-derived long-chain fatty acids via extracellular vesicles. This lipid uptake, facilitated through CD36, not only fuels these macrophages but also triggers liver metastasis.

¹⁹⁷

macrophages

Lipid-associated macrophages (LAMs) are enriched in metastasis-bearing lungs and show increased expression of genes related to lipid metabolism, extracellular matrix remodeling, and immunosuppression, indicating a possible role for these cells in promoting cancer progression.

¹⁹⁸

mesenchymal cells

Neutrophils interact with lung mesenchymal cells (MCs), accumulate neutral lipids by inhibiting the activity of adipose triglyceride lipase, and transport lipids to metastatic tumor cells through the macrophage-lysosomal pathway, enhancing the survival and proliferation capabilities of tumor cells, thereby promoting metastatic colonization of the lungs.

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CAFs

CRC cells, through their exosomes rich in HSPC111, impacted liver metastasis by reprogramming the lipid metabolism of liver CAFs.

¹⁰⁷

CAFs

CAFs triggered lipid metabolism reprogramming by upregulating FASN, increasing the production of lipid metabolites, and promoting the migration of CRC cells through these products.

²⁰⁰

CAFs

Phosphatidylcholine containing unsaturated fatty acid chains secreted by CAFs increased the membrane fluidity of CRC cells and promotes sugar uptake and metabolism, thereby enhancing peritoneal metastasis.

²⁰¹

Arginine metabolism

VIPR1

Activating VIPR1 with VIP led to an increase in ASS1, an enzyme vital for arginine biosynthesis, and this pathway played a critical role in the suppression of HCC growth and metastasis.

²⁰²

FOXO3a

FOXO3a levels are inversely correlated with ASS1 and ASL across different tumor stages, impacting both esophageal squamous cell growth and metastasis.

²⁰³

RIOK3

RIOK3 boosted the expression of the arginine transporter SLC7A2, promoting cell invasion and metastasis in PDAC.

²⁰⁴

HN-HFPA

A multifunctional nanoplatform (HN-HFPA) modulated arginine metabolism in TAMs within TNBC, enhancing immune responses and inhibiting tumor growth through targeted release of L-arginine and L-norvaline.

²⁰⁵

Glutamine metabolism

GOT2

GOT2 silencing promoted reprogramming of glutamine metabolism and sensitized HCC to glutaminase inhibitors.

²⁰⁶

ANGPTL4

ANGPTL4 altered glutamine usage and fatty acid oxidation and influences energy metabolism and tumor spread in NSCLC.

²⁰⁷

glutamine

Inhibition of glutamine metabolism decreased the generation and recruitment of MDSCs and promoted the transformation of TAMs towards an antitumor phenotype.

²⁰⁸

Serine metabolism

ZEB1

ZEB1 reprogrammed the de novo serine synthesis pathway by transcriptionally activating PHGDH, thus promoting carcinogenesis and metastasis in HCC.

²⁰⁹

PSPH

PSPH promoted melanoma growth and metastasis by metabolic deregulation-mediated transcriptional activation of NR4A1.

²¹⁰

PHGDH

Modification of PHGDH by a protein complex increased serine and S-adenosylmethionine levels, enhancing gene expression for cell adhesion and promoting CRC metastasis.

²¹¹

Asparagine metabolism

DON

Glutamine mimicry suppressed tumor progression through asparagine metabolism in PDAC.

²¹²

NUCKS1

NUCKS1increased the levels of asparagine by promoting the expression of ASNS, and this rise in asparagine fuels the growth and spread of osteosarcoma cells.

²¹³

ASNS

ASNS was found to be highly expressed in oral squamous cell carcinoma, correlating positively with lymph node metastasis and perineural invasion.

²¹⁴