OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2

Ye, Gang; Xiong, Guangbing; Feng, Mengyu; Zhao, Fangyu; Qiu, Jiangdong; Liu, Yueze; Cao, Zhe; Wang, Huanyu; Yang, Jinshou; You, Lei; Zheng, Lianfang; Zhang, Taiping; Zhao, Yupei

doi:10.1158/1541-7786.mcr-19-0718

Cited by 46 publications

(32 citation statements)

References 36 publications

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“…Recently, a study has deepened the pathway involved in LOX-1-induced-PC metastasis [ 58 ]. The whole transcriptome RNA-sequencing analysis of pancreatic adenocarcinoma cells in which OLR1 has been overexpressed or inhibited was performed.…”

Section: Lox-1 and Pancreatic Cancermentioning

confidence: 99%

LOX-1 and cancer: an indissoluble liaison

et al. 2021

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Recently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on metabolic targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for the recognition, binding, and internalization of ox-LDL. In the past, several studied, aimed to clarify the role of LOX-1 receptor in atherosclerosis, shed light on its role in the stimulation of the expression of adhesion molecules, pro-inflammatory signaling pathways, and pro-angiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells and macrophages. In recent years, LOX-1 upregulation in different tumors evidenced its involvement in cancer onset, progression and metastasis. In this review, we outline the role of LOX-1 in tumor spreading and metastasis, evidencing its function in VEGF induction, HIF-1alpha activation, and MMP-9/MMP-2 expression, pushing up the neoangiogenic and the epithelial–mesenchymal transition process in glioblastoma, osteosarcoma prostate, colon, breast, lung, and pancreatic tumors. Moreover, our studies contributed to evidence its role in interacting with WNT/APC/β-catenin axis, highlighting new pathways in sporadic colon cancer onset. The application of volatilome analysis in high expressing LOX-1 tumor-bearing mice correlates with the tumor evolution, suggesting a closed link between LOX-1 upregulation and metabolic changes in individual volatile compounds and thus providing a viable method for a simple, non-invasive alternative monitoring of tumor progression. These findings underline the role of LOX-1 as regulator of tumor progression, migration, invasion, metastasis formation, and tumor-related neo-angiogenesis, proposing this receptor as a promising therapeutic target and thus enhancing current antineoplastic strategies.

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Section: Lox-1 and Pancreatic Cancermentioning

confidence: 99%

LOX-1 and cancer: an indissoluble liaison

et al. 2021

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“…A previous study showed that OLR1 is a lectin-like scavenger receptor. This receptor binds to several ligands, such as oxidized low-density lipoprotein, polyanionic chemicals, and anionic phospholipids [ 47 ]. Aberrant expression of O LR1 has been reported in multiple cancers; its expression induces the release of inflammatory cytokines and is closely related to cancer development and metastasis [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

Koma

Asai

Minemura

et al. 2021

IJMS

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We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.

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“…For example, long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) promotes HMGA2 expression by sponging miR-532-3p in non-small cell lung cancer (NSCLC) cells [31]. Oxidized low density lipoprotein receptor 1 (OLR1) increased HMGA2 transcription by upregulating c-Myc expression in pancreatic cancer cells [32]. However, the mechanism underlying which regulates the transcriptional expression of HMGA2 in hepatocellular carcinoma cells remains largely unclear.…”

Section: Discussionmentioning

confidence: 99%

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

Liang

Niu

Wang

et al. 2020

Preprint

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Abstract Background High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism of HMGA2 transcriptional regulation in hepatocellular carcinoma cells remains largely unclear. Methods Mouse model of lung metastasis was used to evaluate the effects of HMGA2 on hepatocellular carcinoma. DEN-induced rat model of hepatocellular carcinoma was used to measure the expression of HMGA2 and histone H3 acetylation. Immunohistochemistry was used to analyze the expression levels of HMGA2 in 39 matched HCC tissues and adjacent non-tumor tissues. Real-time PCR, Western blotting and Chromatin Immunoprecipitation assay were used to investigate the underlying mechanisms by which HMGA2 overexpression in hepatocellular carcinoma cells. Result Compared with adjacent non-tumour tissues, the expression of HMGA2 was significantly upregulated in human HCC tumor tissues. Moreover, We demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in human HCC specimens. Conclusion p300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma.

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OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2

Cited by 46 publications

References 36 publications

LOX-1 and cancer: an indissoluble liaison

LOX-1 and cancer: an indissoluble liaison

Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

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