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 20 publications

(6 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 results displayed that the PF and LAQ combination could significantly inhibit HCT116 cell line migration (Figure 4A). Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) are matrix metalloproteases involved in cancer progression and invasion, and their expression is considered a marker of cell invasiveness [35]. We performed Western blot analysis to test the levels of MMP2 and MMP9.…”

Section: Combined Treatment Of Laq and Pf Synergistically Inhibited I...mentioning

confidence: 99%

Inhibition of Notch Signaling Enhances Antitumor Activity of Histone Deacetylase Inhibitor LAQ824

Mei,

Xu,

Gao

et al. 2023

IJMS

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As a novel histone deacetylase inhibitor (HDACi), LAQ824 (LAQ) effectively inhibits the proliferation of hematological malignancies and solid tumors. However, phase II trials of LAQ in solid tumors were terminated due to dose-dependent toxicity. Furthermore, LAQ has been shown to induce the activation of the Notch signaling pathway in hematopoietic stem cells, which is associated with tumor progression and drug resistance in colon and breast cancers. Therefore, in this study, we investigated the strategy of LAQ combined with a Notch signaling pathway inhibitor to treat solid tumors. We used RT-PCR and Western blot methods to demonstrate that LAQ upregulated the Notch signaling pathway in solid tumor cell lines at the molecular level. The combination of LAQ and a Notch signaling pathway inhibitor was shown by a Chou–Talalay assay to have a synergistic effect in inhibiting solid tumor cell line proliferation in vitro. We also demonstrated that the combination of LAQ and a Notch signaling pathway inhibitor significantly inhibited the growth of tumor cells in vivo using an allograft tumor model. This study indicates that inhibition of the Notch signaling pathway provides a valuable strategy for enhancing solid tumor sensitivity to LAQ.

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ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer

Cited by 20 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

Inhibition of Notch Signaling Enhances Antitumor Activity of Histone Deacetylase Inhibitor LAQ824

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