C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake

Wang, Dongmei; Cheng, Xinghua; Li, Yu; Guo, Mingwei; Zhao, Wenjun; Qiu, Jin; Zheng, Ying; Meng, Meiyao; Ping, Xiaodan; Chen, Xin; Wang, Shu; Luo, Jian; Luo, Qingquan; Ma, Xinran; Xu, Lingyan

doi:10.1038/s41388-019-1015-z

Cited by 23 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cancer cells undergo significant lipid metabolic reprogramming to ensure sufficient energy supply for survival and progression. In a present study, Wang et al [28] demonstrated that C/EBP δ , a critical lipid metabolic regulator, is a TGF- β 1 downstream gene and promotes lung adenocarcinoma metastasis. Importantly, C/EBP δ caused significant oscillations in both lipid metabolic and epithelial to mesenchymal transition (EMT) gene networks.…”

Section: Discussionsupporting

confidence: 48%

BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

Shu

Wang

Han

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

Metastasis is the leading cause of lung cancer-associated death. Downregulated expression of E-cadherin followed by epithelial-mesenchymal transition (EMT) is critical for metastasis initiation in lung cancer. BTBD7 plays essential roles in lung cancer metastasis, but the mechanisms remain unknown. This study aimed to investigate the relationship between BTBD7 and E-cadherin in lung cancer and explore the role of BTBD7 in EMT. Fresh lung cancer and paracancer tissue specimens were collected from 30 patients, and the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin was analyzed by qRT-PCR, western blotting, and immunohistochemistry. A549 and HBE cells were cultured and treated with TGF-β1 for 72 h to induce EMT. Western blotting and qRT-PCR were performed to evaluate the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin. Then, A549 cells were treated separately with the BTBD7-ENTER plasmid, BTBD7-siRNA, and paclitaxel. After TGF-β1-induced EMT, the abovementioned markers were analyzed by western blotting and qRT-PCR. Wound healing assays were applied to assess the migration ability of cells in different groups. For animal experiments, A549 cells transfected with the BTBD7-ENTER plasmid were transplanted into BALB/c nude mice. After 4 weeks, all nude mice were sacrificed, and tumor tissues were harvested for qRT-PCR, western blot, and immunohistochemical analyses of the abovementioned markers. All experimental results showed that the levels of BTBD7, N-cadherin, fibronectin, and vimentin were increased in lung cancer tissues and cells, while the E-cadherin level was decreased. Transfection experiments showed that BTBD7 inhibited E-cadherin expression and enhanced EMT. Moreover, the migration capacity of lung cancer cells was increased by the high level of BTBD7. We concluded that BTBD7 is highly expressed during lung cancer development and metastasis and can inhibit the expression of E-cadherin and promote EMT in lung cancer. BTBD7 may thus be a therapeutic target for lung cancer.

show abstract

Section: Discussionsupporting

confidence: 48%

BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

Shu

Wang

Han

et al. 2019

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Wang et al demonstrated that C/EBP6 was able to recruit oncogene NCOA3 that consequently transcriptionally activates slug. It is a canonical EMT transcription factor that stimulates the uptake of oxLDL to promote metastasis [ 60 ]. According to Khaidakov and Mehta, LDL-C can activate NADPH oxidase and increase the production of superoxide [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Lipoproteins as Markers for Monitoring Cancer Progression

Maran

Hamid

2021

Journal of Lipids

View full text Add to dashboard Cite

Lipoproteins are among the contributors of energy for the survival of cancer cells. Studies indicate there are complex functions and metabolism of lipoproteins in cancer. The current review is aimed at providing updates from studies related to the monitoring of lipoproteins in different types of cancer. This had led to numerous clinical and experimental studies. The review covers the major lipoproteins such as LDL cholesterol (LDL-C), oxidized low-density lipoprotein cholesterol (oxLDL-C), very low-density lipoprotein cholesterol (VLDL-C), and high-density lipoprotein cholesterol (HDL-C). This is mainly due to increasing evidence from clinical and experimental studies that relate association of lipoproteins with cancer. Generally, a significant association exists between LDL-C with carcinogenesis and high oxLDL with metastasis. This warrants further investigations to include Mendelian randomization design and to be conducted in a larger population to confirm the significance of LDL-C and its oxidized form as prognostic markers of cancer.

show abstract

“…However, in HNC cell lines, these oxLDL endocytic mechanisms are unknown. Some studies have already investigated oxLDL involvement in prostate, colorectal and lung cancer, which all demonstrated that oxLDL promotes cancer metastasis via Lox-1 activation in vitro and in vivo [ 26 , 27 , 28 ]. Notably, Gonzalez et al demonstrated, in prostate cancer, a significant increase in Lox-1 expression in adenocarcinoma compared to normal prostate tissue [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Oxidized Low-Density Lipoprotein on Head and Neck Squamous Cell Carcinomas

et al. 2021

View full text Add to dashboard Cite

Cardiovascular disease (CVD) and cancer are two major causes of death worldwide. The question is, “Could there be a link between these two pathologies in addition to their shared, common risk factors?” To find some answers, we studied the effect of oxidized low-density lipoproteins (oxLDL) on head and neck cancer (HNC) cell lines, since oxLDL is a major contributor to atherosclerosis and the principal cause of CVD. In this study, we exposed three HNC cell lines (Detroit 562, UPCI-SCC-131 and FaDu) to oxLDL. We investigated two oxLDL receptors, CD36 and Lox-1, using immunofluorescence. Cancer cell migration was evaluated using Boyden chambers and the Wnt/β-catenin pathway was investigated using Western blotting. We demonstrated that the expression of CD36 and Lox-1 significantly increases after exposure to oxLDL. Moreover, we found that oxLDL reduces the migration of HNC cell lines, an observation that is in line with an increased degradation of β-catenin under oxLDL. Finally, the inhibition of CD36 with sulfosuccinimidyl oleate (SSO) reverses the inhibition of cell migration. In conclusion, we report that oxLDL seems to induce an increase in CD36 expression on HNC cell lines, enhancing the uptake of these lipids in cells to finally decrease cancer cell migration via the CD36/β-catenin pathway.

show abstract

C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake

Cited by 23 publications

References 41 publications

BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

Lipoproteins as Markers for Monitoring Cancer Progression

Effect of Oxidized Low-Density Lipoprotein on Head and Neck Squamous Cell Carcinomas

Contact Info

Product

Resources

About