NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells

Zhou, Ya; Zhu, Yuanyuan; Fan, Xiaoyan; Zhang, Chundong; Wang, Ying; Zhang, Lian; Zhang, Huan; Wen, Tao; Zhang, Kaina; Huo, Xiao; Jiang, Xue; Bu, Youquan; Zhang, Ying

doi:10.18632/oncotarget.16145

Cited by 49 publications

(52 citation statements)

References 40 publications

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“…Thus, NID1 has been shown to promote tumor cell migration, invasion, and chemoresistance in ovarian carcinomas via the induction of Epithelial-Mesenchymal Transition (EMT). 66 Another study revealed a possible NID1 involvement in the acquisition of migratory and invasive properties by endometrial cancer cells. 67 It has also been shown that NID1 was present at high levels in the secretome of lung metastases in both breast cancer and melanoma.…”

Section: Discussionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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Section: Discussionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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“…As a secreted pro-metastatic protein, NID1 has been reported to promote lung metastasis of breast cancer and melanoma 35 . Zhou et al 20 also showed that NID1 promoted EMT of ovarian cancer cells through activating extracellular-signal-regulated kinase/mitogen-activated protein kinase signaling. Here, in our study, JQ1 obviously reduced the mRNA and protein expression of NID1 in all GC cells and NID1 was necessary for JQ1-inducing suppression of GC cell migration and invasion validated by rescue experiments.…”

Section: Discussionmentioning

confidence: 98%

“…4e). Among the 40 mostly dysregulated genes upon JQ1 treatment, we chose NID1 as the target gene, because NID1 has been reported to promote cancer metastasis in various cancer types 20 (Fig. 4f).…”

Section: Jq1 Significantly Reduces the Expression Of Nid1 In Gc Cellsmentioning

confidence: 99%

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BET protein inhibitor JQ1 downregulates chromatin accessibility and suppresses metastasis of gastric cancer via inactivating RUNX2/NID1 signaling

et al. 2020

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Chromatin accessibility is critical for tumor development, whose mechanisms remain unclear. As a crucial regulator for chromatin remodeling, BRD4 promotes tumor progression by regulating multiple genes. As a small-molecule inhibitor of BRD4, JQ1 has potent chemotherapeutic activity against various human cancers. However, whether JQ1 has potential anti-tumor effects and how JQ1 regulates global transcription in gastric cancer (GC) remain largely unknown. In this research, we found BRD4 was highly expressed in GC tissues and was significantly associated with poor prognosis. JQ1 inhibited the proliferation and induced apoptosis of GC cells in vitro. Besides, JQ1 suppressed the migration and invasion of cancer cells by inducing MET. Notably, an assay for transposase-accessible chromatin using sequencing (ATAC-seq) data showed that JQ1 obviously downregulated the chromatin accessibility of GC cells and differentially accessible regions were highly enriched for RUNX2-binding motifs. Combinational analysis of ATAC-seq and RNA-seq data discovered NID1 as the downstream target of JQ1 and JQ1 reduced NID1 expression in GC cells. Chromatin immunoprecipitation, luciferase reporter gene assay, and rescue experiments all confirmed that RUNX2/NID1 axis was responsible for JQ1-inhibiting metastasis of GC cells. What's more, high expression of NID1 in GC tissues also predicted poor survival outcome of cancer patients and NID1 knockdown prohibited migration and invasion of cancer cells via partially inducing MET. Finally, in vivo models showed that JQ1 prevented GC growth and suppressed cancer metastasis. In conclusion, JQ1 inhibits the malignant progression of GC by downregulating chromatin accessibility and inactivating RUNX2/NID1 signaling. In addition, NID1 is also a novel therapeutic target for progressive GC patients. Oncogenesis 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,;

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“…It is a serious disease particularly when it is in its advanced stages with a course that is punctuated by frequent tumour recurrence and negative impact on quality and length of life [1]. Despite enormous efforts, there are no successful screening methods developed until now to decrease mortality, whether by pelvic examination, ultrasonography or by use of serum markers.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Serum Nidogen-2 as a Screening and Diagnostic Tool for Ovarian Cancer

Torky

Sherif

Abo-Louz

et al. 2017

Gynecol Obstet Invest

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Introduction: Ovarian cancer is a relatively common occurrence with the formation of a tumour in the ovaries and is the leading cause of death in the gynecological field. Despite enormous efforts, there are no successful screening methods developed until now to decrease mortality in this regard. Aim: To evaluate nidogen-2 as a new tumour marker combined with higher sensitivity, specificity and accuracy than carbohydrate antigen (CA-125) and Doppler ultrasound to improve early diagnosis of ovarian cancer. Patients and Methods: One hundred and forty-four qualified women with a preliminary diagnosis of adnexal mass were subjected to history, examination, transvaginal Doppler ultrasound and Quantitative assessment of serum level of CA-125 and nidogen-2 followed by the resection of the masses, which were sent for histopathological examination. Results: One-hundred and sixteen cases were benign and 28 cases were malignant. The surgical procedures ranged from limited resection to radical hysterectomy. There was a highly significant correlation between both serum nidogen-2 and CA-125 and the results of histopathological examination (p = 0.0001). Serum nidogen-2 had 91.6% sensitivity, 62% specificity, 37.1% positive predictive value, 97.9% negative predictive value and 68% accuracy (p < 0.05). Conclusion: Nidogen-2 is a new promising ovarian malignancy biomarker that correlates closely with ultrasound and CA125. It did improve the accuracy of diagnosis, but further studies are needed.

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NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells

Cited by 49 publications

References 40 publications

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

BET protein inhibitor JQ1 downregulates chromatin accessibility and suppresses metastasis of gastric cancer via inactivating RUNX2/NID1 signaling

Evaluation of Serum Nidogen-2 as a Screening and Diagnostic Tool for Ovarian Cancer

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