ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Sun, Jiawei; Zhang, Zizheng; Chen, Jingyu; Xue, Min; Pan, Xia

doi:10.7150/ijbs.62293

Cited by 15 publications

(4 citation statements)

References 31 publications

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“…For example, retinoic acid α promotes CRC carcinogenesis by increasing MMP2 transcription, 25 and seven transmembrane domains containing 1 (ELTD1/ ADGRL4) can promote CRC cell migration and invasion by activating MMP2 at the transcriptional level. 11 Furthermore, TWIST1/2 can bind to the MMP2 promoter and induce its expression, resulting in increased epithelial-tomesenchymal transition and invasion potential of CRC cells. 26 In the present study, HaploReg v4.1 27 was used to investigate possible SNP functional effects.…”

Section: Discussionmentioning

confidence: 99%

“… 9 MMP2 maps to chromosome 16q12.2 and is a member of the MMP family whose protein product, type IV collagenase, can degrade various collagen substrates, including fibronectin, aggrecan, elastin, and nidogen, among others; this can contribute to tumor development by influencing cancer cell invasion and migration. 10 , 11 Furthermore, MMP2 gene polymorphisms are associated with risk for multiple diseases. The rs2241146 single nucleotide polymorphism (SNP) in MMP2 is associated with an increased risk of steroid-induced osteonecrosis of the femoral head in the Chinese Han population, 12 while another MMP2 SNP, rs243865, is not associated with susceptibility to breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

Liu¹,

Yang²,

Li³

et al. 2022

IJGM

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Colorectal cancer (CRC) is among the most common cancers worldwide and an important cause of cancer-related death. Inherited genetic variation plays a vital role in the occurrence and development of CRC. The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in MMP2 with CRC risk. Patients and Methods: Three candidates, MMP2 SNPs, rs1053605, rs243849, and rs14070, were selected and genotyped using the Agena MassARRAY RS1000 system, and their association with risk of CRC was evaluated in 663 CRC cases and 663 healthy controls by calculating odds ratio (OR) with 95% confidence interval (95% CI) values. Results:The minor allele of rs243849 (T) was significantly less frequent in cases than controls (p = 0.021), and this SNP was associated with a decreased risk of CRC under co-dominant (p = 0.033), dominant (p = 0.021), and log-additive (p = 0.017) models, after adjusting for confounding factors. After stratification, rs243849 was found to be protective against CRC in patients who were non-smoking, consumed alcohol, and were ≥60 years old (p < 0.05). Conversely, rs1053605 was associated with disease occurrence in patients with CRC who consumed alcohol and were <60 years old (p < 0.05). Furthermore, rs1053605 genotype was associated with an increased risk of colon cancer (p < 0.05), while that of rs243849 was associated with a decreased risk of rectal cancer (p < 0.05). The rs1053605-rs243849 CT haplotype exhibited a protective role in CRC risk, following adjustment for confounders (p = 0.014). The rs14070 SNP was not associated with CRC risk. Finally, the false discovery rate (FDR) method was used to validate the study results. Conclusion: Overall, the MMP2 gene polymorphisms, rs243849 and rs1053605, may be useful for predicting CRC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

Liu¹,

Yang²,

Li³

et al. 2022

IJGM

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“…GPR116/ADGRF5 plays a critical role in promoting breast cancer progression and metastasis through the p63RhoGEF-RhoA/Rac1 signaling pathway [ 44 ]. High ELTD1/ADGRL4 expression is linked to LNM and poor outcomes in patients with CRC [ 45 ]. However, the Cancer Genome Atlas reported EMR1 expression in CRC but did not consider it as a prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer

et al. 2022

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EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was found in 91 (22.8%) of the 399 CRC samples tested by immunohistochemical staining and showed a significant relationship with lymph node metastasis. Furthermore, EMR1-TC was significantly associated with CD68+ CD163+ tumor-associated macrophages (TAMs), and CRC with a high combined EMR1-TC+CD68+CD163+ score showed worse recurrence-free survival prognosis. In an in vitro co-culture assay of colon cancer cells with myeloid cells, we found that EMR1 expression significantly upregulated in cancer cells was induced by macrophages. In addition, there was increased expression of M2 markers (CD163 and interleukin-6 & 10) in myeloid portion, while that of M1 markers (CD86 and iNOS) remained unchanged. Accordingly, upon treatment with M2 macrophage polarization inhibitors (O-ATP, trametinib, bardoxolone methyl), EMR1 expression reduced significantly, along with M2 markers (CD163 and interleukin-6 & 10). In conclusion, EMR1-TC was a high-risk factor for lymph node metastasis and correlated with poor recurrence free survival, particularly in patients with TAM-rich CRC. Furthermore, EMR1 expression in colon cancer cells may be related to M2 macrophage polarization and vice versa.

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“…The five-year survival rate for regional CRC is approximately 72%; however, metastasis reduces the survival rate to 15% [ 8 ]. Metastasis is a key factor affecting CRC treatment and prognosis, and patients who develop metastasis have limited treatment options and a poor prognosis [ 9 ]. Exploring the mechanisms by which metastasis occurs in CRC may provide new treatment options for patients with metastatic colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

Wang

Huang

et al. 2022

Cells

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Colorectal cancer (CRC) is a malignancy that seriously threatens human health, and metastasis from CRC is a major cause of death and poor prognosis for patients. Studying the potential mechanisms of small extracellular vesicles (sEVs) in tumor development may provide new options for early and effective diagnosis and treatment of CRC metastasis. In this review, we systematically describe how sEVs mediate epithelial mesenchymal transition (EMT), reconfigure the tumor microenvironment (TME), modulate the immune system, and alter vascular permeability and angiogenesis to promote CRC metastasis. We also discuss the current difficulties in studying sEVs and propose new ideas.

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ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Cited by 15 publications

References 31 publications

MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

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