Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

Qiu, Zhendong; Deng, Wen-feng; Hong, Yupu; Zhao, Liang; Li, Man; Guan, Yongjun; Su, Ying-ru; Chen, Chen; Shi, Qiao; Yu, Jia; Wang, Weixing

doi:10.2147/ott.s282906

Cited by 9 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies reported that supplementation with whey protein concentrate selectively depletes tumor GSH levels [32].The reduction of GSH levels has been shown to regulate both extrinsic and intrinsic apoptotic signaling cascades at different checkpoints [37]. The in vitro protective effects of whey occur also through a negative regulation of SREBP1 whose elevated activity has been implicated in the tumorigenesis of CRC [38,39]. Indeed, SREBP1 gene silencing has been shown to inhibit CRC cell proliferation, migration, and invasion and promote apoptosis [38,39].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells

Martino

Balestrieri

Mele

et al. 2021

Cancers

View full text Add to dashboard Cite

Emerging strategies to improve healthy aging include dietary interventions as a tool to promote health benefits and reduce the incidence of aging-related comorbidities. The health benefits of milk are also linked to its richness in betaines and short-chain acylcarnitines, which act synergistically in conferring anticancer, anti-inflammatory, and antioxidant properties. Whey, despite being a dairy by-product, still has a considerable content of bioactive betaines and acylcarnitines. Here, we investigated the anticancer properties of whey from Mediterranean water buffalo (Bubalus bubalis) milk by testing its antiproliferative effects in colorectal cancer (CRC) cells HT-29, HCT 116, LoVo and SW480. Results indicated that treatment with whey for 72 h inhibited cell proliferation (p < 0.001), induced cell cycle arrest, and apoptosis via caspase-3 activation, and modulated cell metabolism by limiting glucose uptake and interfering with mitochondrial energy metabolism with the highest effects observed in HT-29 and HCT 116 cells. At molecular level, these effects were accompanied by upregulation of sirtuin 3 (SIRT3) (p < 0.01) and peroxisome proliferator-activated receptor (PPAR)-γ expression (p < 0.001), and downregulation of lactate dehydrogenase A (LDHA) (p < 0.01), sterol regulatory-element binding protein 1 (SREBP1) (p < 0.05), and PPAR-α (p < 0.01). Transient SIRT3 gene silencing blocked the effects of whey on the LDHA, PPAR-γ, and PPAR-α protein expressions (p < 0.01) suggesting that the whey capacity of perturbating the metabolic homeostasis in CRC cell lines is mediated by SIRT3.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The in vitro protective effects of whey occur also through a negative regulation of SREBP1 whose elevated activity has been implicated in the tumorigenesis of CRC [38,39]. Indeed, SREBP1 gene silencing has been shown to inhibit CRC cell proliferation, migration, and invasion and promote apoptosis [38,39].…”

Section: Discussionmentioning

confidence: 99%

SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells

Martino

Balestrieri

Mele

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…The colocalization of SREBP-1 and FASN is found in CRC tissues, and the transcriptional regulation of SREBP-1 on the FASN promoter can respond to the deficiency in endogenous fatty acid synthesis in colorectal neoplasia ( 62 ). Moreover, the combination of SREBP-1 and ACLY can significantly promote CRC cell proliferation, migration, and invasion, which is mediated by lipid synthesis modulation ( 63 ). In addition, the overexpression of SREBP-1 promotes the angiogenesis and invasion of CRC cells by promoting MMP-7 expression related to NF-κB p65 phosphorylation ( 61 ).…”

Section: Colorectal Cancermentioning

confidence: 99%

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

2022

View full text Add to dashboard Cite

Sterol regulatory element binding protein-1 (SREBP-1), a transcription factor with a basic helix–loop–helix leucine zipper, has two isoforms, SREBP-1a and SREBP-1c, derived from the same gene for regulating the genes of lipogenesis, including acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase. Importantly, SREBP-1 participates in metabolic reprogramming of various cancers and has been a biomarker for the prognosis or drug efficacy for the patients with cancer. In this review, we first introduced the structure, activation, and key upstream signaling pathway of SREBP-1. Then, the potential targets and molecular mechanisms of SREBP-1-regulated lipogenesis in various types of cancer, such as colorectal, prostate, breast, and hepatocellular cancer, were summarized. We also discussed potential therapies targeting the SREBP-1-regulated pathway by small molecules, natural products, or the extracts of herbs against tumor progression. This review could provide new insights in understanding advanced findings about SREBP-1-mediated lipogenesis in cancer and its potential as a target for cancer therapeutics.

show abstract

“…Consistent with these findings, the data of our integrated analysis showed that fatty acid (FA) transportation and beta-oxidation were enhanced in thyroid carcinoma. Lipids supply the primary structural FAs and glycerides of biological plasma membrane, and provide potential energy substrates, which support rapid tumour proliferation ( 27 ). Previously, we have demonstrated that the levels of FAs were significantly low in patients with thyroid carcinoma ( 13 , 14 ).…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma

et al. 2021

View full text Add to dashboard Cite

ObjectivePapillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancer and affects a large number of individuals. The pathogenesis of PTC has not been completely elucidated thus far. Metabolic reprogramming is a common feature in tumours. Our previous research revealed the reprogramming of lipid metabolism in PTC. Further studies on lipid metabolism reprogramming may help elucidate the pathogenesis of PTC.MethodsClinical samples of PTC and para-tumour tissue were analysed using lipidomic, proteomic, and metabolomic approaches. A multi-omics integrative strategy was adopted to identify the important pathways in PTC. The findings were further confirmed using western blotting, tissue microarray, bioinformatics, and cell migration assays.ResultsMulti-omics data and the results of integrated analysis revealed that the three steps of fatty acid metabolism (hydrolysis, transportation, and oxidation) were significantly enhanced in PTC. Especially, the expression levels of LPL, FATP2, and CPT1A, three key enzymes in the respective steps, were elevated in PTC. Moreover, LPL, FATP2 and CPT1A expression was associated with the TNM stage, lymph node metastasis of PTC. Moreover, high levels of FATP2 and CPT1A contributed to poor prognosis of PTC. In addition, ectopic overexpression of LPL, FATP2 and CPT1A can each promote the migration of thyroid cancer cells.ConclusionsOur data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for PTC progression. This may help elucidating the underlying mechanism of PTC pathogenesis and identifying the potential therapeutic targets for PTC.

show abstract

Biological Behavior and Lipid Metabolism of Colon Cancer Cells are Regulated by a Combination of Sterol Regulatory Element-Binding Protein 1 and ATP Citrate Lyase

Cited by 9 publications

References 36 publications

SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells

SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells

Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

Multi-Omics Analysis of Fatty Acid Metabolism in Thyroid Carcinoma

Contact Info

Product

Resources

About