Activating transcription factor 1 promoted migration and invasion in lung cancer cells through regulating EGFR and MMP‐2

Cui, Jinggang; Yin, Zi-Xin; Li, Guohua; Chen, Xiaojun; Xiao-lai, Gao; Lü, Huiling; Li, Wei; Lin, Dong

doi:10.1002/mc.23086

Cited by 15 publications

(14 citation statements)

References 21 publications

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“…Activated transcription factor 1 (ATF1) plays an important role in the migration and invasion of lung cancer cells. A study proposed that the silencing of ATF1 can induce the down-regulation of MMP2 expression, thereby inhibiting the migration and invasion of lung cancer cells [ 23 ]. Recent publications and clinical trials have emphasized the potential value of measuring circulating or tissue MMP-2 levels as a tool for tumor diagnosis or prognosis prediction, or as a primary therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Correlation between MMP2 expression in lung cancer tissues and clinical parameters: a retrospective clinical analysis

et al. 2020

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Background Matrix metalloproteinase 2 (MMP2) has been found to be related to malignant tumors; the aim of this study was to investigate the correlation between MMP2 expression in lung cancer tissues and clinical parameters of lung cancer. Methods The expression of MMP2 in lung cancer tissues and in adjacent non-malignant tissues was tested by immunohistochemistry. The correlation between the expression of MMP2 and clinical parameters of lung cancer was analyzed by Kaplan-Meier curve and multiple regression analysis. Results The expression of MMP2 was higher in lung cancer tissues than that in adjacent non-malignant tissues (p = 0.002). Increased MMP2 was associated with low differentiation (p = 0.022), tumor size (p = 0.032), lymph node metastasis (p < 0.001), advanced stage (p = 0.002). The post-surgical survival time in patients with high MMP2 expression was shorter than that in patients with low MMP2 expression (p = 0.001). High expression of MMP2 (p = 0.006) and advanced stage (p = 0.003) were independent prognostic indicators for survival of lung cancer patients. Conclusions Increased MMP2 correlates with malignant biological behavior of lung cancer and it could be a potential biomarker for diagnosis and prognosis of the disease.

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Section: Discussionmentioning

confidence: 99%

Correlation between MMP2 expression in lung cancer tissues and clinical parameters: a retrospective clinical analysis

et al. 2020

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“…Our most significant findings at 24 hours include that GREM2 mutant cells (T allele) migrated less/slower and proliferated less than those with the reference allele; whereas ATF1 T allele‐transfected cells presented increased cell migration and proliferation when compared to the C allele. In this context, numerous studies showed that ATF1 overexpression resulted in increased cell proliferation in various cancers 20,32,33 . However, those effects seem to be site‐specific, as other studies demonstrate that ATF1 might also act as a tumour suppressor such as in breast cancer 34 .…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of ATF1, GREM2 AND WNT10B variants associated with tooth agenesis

Williams

Zeng

Chiquet

et al. 2021

Orthod Craniofacial Res

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Objective To determine the functional effects of ATF1, WNT10B and GREM2 gene variants identified in individuals with tooth agenesis (TA). Settings and sample population Stem cells from human exfoliated deciduous teeth (SHED) were used as an in vitro model system to test the effect of TA‐associated variants. Materials and methods Plasmid constructs containing reference and mutant alleles for ATF1 rs11169552, WNT10B rs833843 and GREM2 rs1414655 variants were transfected into SHED for functional characterization of variants. Allele‐specific changes in gene transcription activity, protein expression, cell migration and proliferation, and expression of additional tooth development genes (MSX1, PAX9 and AXIN2) were evaluated. Data analyses were performed using Student's t‐test. P‐values ≤ .05 were considered statistically significant. Results Mutant variants resulted in significantly decreased transcriptional activity of respective genes (P < 0.05), although no changes in protein localization were noted. Expression of MSX1 was significantly decreased in ATF1‐ and GREM2‐mutant cells, whereas PAX9 or AXIN2 mRNA expression was not significantly altered. Mutant WNT10B had no significant effect on the expression of additional TA genes. ATF1‐ and GREM2‐mutant cells presented increased cell migration. Cell proliferation was also affected with all three mutant alleles. Conclusions Our results demonstrate that ATF1, WNT10B and GREM2 mutant alleles have modulatory effects on gene/protein function that may contribute to TA.

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“…Overexpression of ATF1 in nasopharyngeal carcinoma was positively correlated with the expression of MMP2. ATF1 led to the increasing level of MMP2 expression as well as promotion in lung cancer cell migration and invasion [ 38 ]. However, previous study did not show which phosphorylated site of ATF1 was important for the regulation.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer

Cao

et al. 2022

J Transl Med

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Background Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). Methods Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. Results High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. Conclusion Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

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Activating transcription factor 1 promoted migration and invasion in lung cancer cells through regulating EGFR and MMP‐2

Cited by 15 publications

References 21 publications

Correlation between MMP2 expression in lung cancer tissues and clinical parameters: a retrospective clinical analysis

Correlation between MMP2 expression in lung cancer tissues and clinical parameters: a retrospective clinical analysis

Functional characterization of ATF1, GREM2 AND WNT10B variants associated with tooth agenesis

Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer

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