Cancer metabolism and tumor microenvironment: fostering each other?

Yuan, Yiyuan; Li, Huimin; Wang, Pu; Chen, Leilei; Guo, Dong; Jiang, Hongfei; He, Bo; Qin, Siyuan; Wang, Kui; Li, Na; Feng, Jingwei; Wen, Jing; Cheng, Shipeng; Zhang, Yaguang; Yang, Weiwei; Ye, Dan; Lu, Zhimin; Huang, Canhua; Mei, Jun; Zhang, Huafeng; Gao, Ping; Jiang, Peng; Su, Shicheng; Sun, Bing; Zhao, Shimin

doi:10.1007/s11427-021-1999-2

Cited by 98 publications

(57 citation statements)

References 444 publications

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“…Proverbially, metabolic reprogram has been associated with multiple stages of cancer progression, including oncogenic transformation, evasion of apoptosis, tumor metastasis and drug resistance [ 27 – 32 ]. Among changes in tumor metabolism, the role of proline metabolism has gradually received increasing attention [ 14 – 16 , 28 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis

Qian

Tong

et al. 2022

Discov Onc

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CircRNAs have been found to play crucial roles in the metabolism and progression of cancers, but their roles and mechanisms in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. This work is aimed to explore the role and mechanism of hsa_circ_0000705 (circ_0000705) in ESCC. Circ_0000705 expression was up-regulated in ESCC tissues and cell lines, and high circ_0000705 expression was correlated with poor survival. Circ_0000705 facilitated cell proliferation, invasion, migration and proline metabolism of ESCC cells. The inhibitory effects of circ_0000705 knockdown on cell invasion, migration and proline metabolism were partly rescued by miR-621 inhibition or PYCR1 over-expression. Furthermore, circ_0000705 expression is negatively correlated with miR-621 expression, and positively correlated with PYCR1 in ESCC tissues. Mechanistically, circ_0000705 acted as a ceRNA by sponging miR-621, thereby facilitating PYCR1 expression in ESCC cells. In conclusion, circ_0000705 promoted proline metabolism and malignant progression of ESCC by regulating the miR‑621/PYCR1 axis.

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Section: Discussionmentioning

confidence: 99%

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis

Qian

Tong

et al. 2022

Discov Onc

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“…To our knowledge, metabolism-related pathways are highly associated with the tumor microenvironment [ 38 , 39 , 40 ]. We further explored the association between immune cell infiltration and LGR4 expression.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of LGR4 in Colon Adenocarcinoma as Potential Diagnostic Biomarker, Therapeutic Target and Promoting Immune Cell Infiltration

Xia

et al. 2022

Biomolecules

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Colon adenocarcinoma is one of the tumors with the highest mortality rate, and tumorigenesis or development of colon adenocarcinoma is the major reason leading to patient death. However, the molecular mechanism and biomarker to predict tumor progression are currently unclear. With the goal of understanding the molecular mechanism and tumor progression, we utilized the TCGA database to identify differentially expressed genes. After identifying the differentially expressed genes among colon adenocarcinoma tissues with different expression levels of LGR4 and normal tissue, protein–protein interaction, gene ontology, pathway enrichment, gene set enrichment analysis, and immune cell infiltration analysis were conducted. Here, the top 10 hub genes, i.e., ALB, F2, APOA2, CYP1A1, SPRR2B, APOA1, APOB, CYP3A4, SST, and GCG, were identified, and relative correlation analysis was conducted. Kaplan–Meier analysis revealed that higher expression of LGR4 correlates with overall survival of colon adenocarcinoma patients, although expression levels of LGR4 in normal tissues are higher than in tumor tissues. Further functional analysis demonstrated that higher expression of LGR4 in colon adenocarcinoma may be linked to up-regulate metabolism-related pathways, for example, the cholesterol biosynthesis pathway. These results were confirmed by gene set enrichment analysis. Immune cell infiltration analysis clearly showed that the infiltration percentage of T cells was significantly higher than other immune cells, and TIMER analysis revealed a positive correlation between T-cell infiltration and LGR4 expression. Finally, COAD cancer cells, Caco-2, were employed to be incubated with squalene and 25-hydroxycholesterol-3-sulfate, and relative experimental results confirmed that the cholesterol biosynthesis pathway involved in modulating the proliferation of COAD tumorigenesis. Our investigation revealed that LGR4 can be an emerging diagnostic and prognostic biomarker for colon adenocarcinoma by affecting metabolism-related pathways.

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“…With extensive reprogramming of metabolic pathways supporting cell survival and growth, cancer cells always exhibit preferential dependence on glycolysis (relative to oxidative phosphorylation) for energy production in an oxygen-independent manner. This is called Warburg effect and plays critical role in tumorigenesis [5]. Although the glycolysis pathway is obviously less efficient than oxidative phosphorylation, regarding the yield of ATP, cancer cells overcome this disadvantage by increasing glucose up-take.…”

Section: Seahorse Metabolic Analysis Also Indicated That Expression O...mentioning

confidence: 99%

“…Metabolic reprogramming is a biochemical hallmark of cancers [5]. Compared with normal cells, cancer cells always exhibit preferential dependence on glycolysis for energy production in an oxygen-independent manner, which is considered as a critical factor to promote tumorigenesis.…”

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confidence: 99%

Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL

Wang¹,

Li²,

Zhou³

et al. 2022

neo

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Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in a human body. The overarching goa l of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but pro moted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.

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Cancer metabolism and tumor microenvironment: fostering each other?

Cited by 98 publications

References 444 publications

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis

Circ_0000705 facilitates proline metabolism of esophageal squamous cell carcinoma cells by targeting miR-621/PYCR1 axis

Bioinformatics Analysis of LGR4 in Colon Adenocarcinoma as Potential Diagnostic Biomarker, Therapeutic Target and Promoting Immune Cell Infiltration

Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL

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