Metabolic cross-talk between ovarian cancer and the tumor microenvironment—providing potential targets for cancer therapy

Lin, Yi; Liang, Xiao; Zhang, Xijie; Ni, Yanghong; Zhou, Xiaoting; Zhao, Xia

doi:10.31083/j.fbl2704139

Cited by 8 publications

(4 citation statements)

References 136 publications

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“…39 Besides, the Warburg effect can transform polar epithelial cells into motile stromal cells, thereby acquiring the ability to migrate. 39 , 40 Therefore, we further explored the effect of Sox11 on the Warburg effect of OSCC cells. The results first revealed that Sox11 overexpression dramatically enhanced glucose uptake and lactate production, and Sox11 knockdown inhibited glucose uptake and lactate production in OSCC cells (Figure 5E,G ).…”

Section: Resultsmentioning

confidence: 99%

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Hypomethylation‐associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP‐associated OSCC

Liu,

Cao,

Xiao

et al. 2024

J Cellular Molecular Medi

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Oral lichen planus (OLP) is a particularly prevalent oral disorder with the potential to progress to oral squamous cell carcinoma (OSCC). SRY‐box transcription factor 11 (Sox11) has been reported to serve as a prognostic marker for various cancers. However, the role and mechanism of Sox11 in OLP‐related OSCC are unknown. Our results indicated that Sox11 was highly expressed, and that Sox11 promoter methylation was significantly reduced in OLP‐associated OSCC tissues. High Sox11 expression and Sox11 promoter hypomethylation indicate a poor patient prognosis. According to in vivo and in vitro experiments, the knockdown of Sox11 inhibited proliferation, invasion, and migration while driving its apoptotic death in OSSC cells; Sox11 overexpression exerted the opposite effect as Sox11 knockdown. Mechanistically, knockdown of Sox11 inhibited PI3K/AKT and glycolysis pathway, and overexpression of Sox11 enhanced the PI3K/AKT and glycolysis pathways in OSCC cells. In addition, we demonstrated that Sox11 overexpression accelerated the progression of OSCC, at least in part by promoting PI3K/AKT pathway activation. In conclusion, our data indicated that the DNA hypomethylation‐associated upregulation of Sox11 could promote oncogenic transformation via the PI3K/AKT pathway in OLP‐associated OSCC. Therefore, Sox11 might be a reliable biomarker for predicting the progression of precancerous oral tissues.

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Section: Resultsmentioning

confidence: 99%

“…Lactate can also promote new angiogenesis and create an environment for tumour cell migration 39 . Besides, the Warburg effect can transform polar epithelial cells into motile stromal cells, thereby acquiring the ability to migrate 39,40 . Therefore, we further explored the effect of Sox11 on the Warburg effect of OSCC cells.…”

Section: Resultsmentioning

confidence: 99%

Hypomethylation‐associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP‐associated OSCC

Liu,

Cao,

Xiao

et al. 2024

J Cellular Molecular Medi

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“…Our analysis revealed asprosin mediated dysregulation of key biological processes and hallmarks of cancer such as: apoptosis, cell proliferation and growth, as well as energy and metabolism [ 52 ]. The tumour microenvironment is known to be modulated by oncogenes which in turn regulate certain aspects of metabolism, ultimately leading to uncontrolled proliferation and metastasis [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

Kerslake

Sisu

Panfilov

et al. 2022

JCM

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Background: Ovarian cancer (OvCa) is one of the most lethal forms of gynaecological malignancy. Altered energy metabolism and increased aerobic glycolysis in OvCa are hallmarks that demand attention. The glucogenic hormone asprosin is often dysregulated in metabolic disorders such as insulin resistance, diabetes (type 2 and gestational), and preeclampsia. Despite association with metabolic disorders, its role in energy metabolism within the tumour microenvironment is yet to be explored. Here, we study the role of asprosin in OvCa using transcriptomics and expand on functional studies with clinical samples. Methods: RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. Results: Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene regulatory changes, at 4 and 12 h respectively, when compared with control samples (p < 0.05 and Log2FC > 1). In addition to energy metabolism and glucose-related pathways, asprosin was shown to alter pathways associated with cell communication, TGF-β signalling, and cell proliferation. Moreover, asprosin was shown to induce phosphorylation of ERK1/2 in the same in vitro model. Using liquid biopsies, we also report for novel expression of asprosin’s predicted receptors OR4M1 and TLR4 in cancer-associated circulating cells; with significant reduction seen between pre-chemotherapy and end of first line chemotherapy, in addition to patients under maintenance with bevacizumab +/− olaparib for OR4M1. Conclusions: In relation to OvCa, asprosin appears to regulate numerous signalling pathways in-vitro. The prognostic potential of OR4M1 in liquid biopsies should also be explored further.

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“…However, a growing number of experimental and clinical data suggest that TAMs play a dual function in tumor growth and survival, and their anti-cancer activity has been partially discovered [ 67 ]. However, TAMs pro- or anti-cancer activity depends on the tumor’s origin site [ 68 ].…”

Section: Metabolic Changes In Tamsmentioning

confidence: 99%

Metabolic Reprogramming in Tumor-Associated Macrophages in the Ovarian Tumor Microenvironment

Kumar

Mittal

Gupta

et al. 2022

Cancers

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The interaction between tumor cells and macrophages in the tumor microenvironment plays an essential role in metabolic changes in macrophages and reprograms them towards a pro-tumorigenic phenotype. Increasing evidence indicates that macrophage metabolism is a highly complex process and may not be as simple as previously thought. Pro-inflammatory stimuli switch macrophages towards an M1-like phenotype and rely mainly on aerobic glycolysis and fatty acid synthesis, whereas anti-inflammatory stimuli switch macrophages towards an M2-like phenotype. M2-like macrophages depend more on oxidative phosphorylation (OXPHOS) and fatty acid oxidation. However, this metabolically reprogrammed phenotypic switch in macrophages remained a mystery for a while. Therefore, through this review, we tend to describe how macrophage immunometabolism determines macrophage phenotypes and functions in tumor microenvironments (TMEs). Furthermore, we have discussed how metabolic reprogramming in TAM can be used for therapeutic intervention and drug resistance in ovarian cancer.

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Metabolic cross-talk between ovarian cancer and the tumor microenvironment—providing potential targets for cancer therapy

Cited by 8 publications

References 136 publications

Hypomethylation‐associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP‐associated OSCC

Hypomethylation‐associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP‐associated OSCC

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

Metabolic Reprogramming in Tumor-Associated Macrophages in the Ovarian Tumor Microenvironment

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