AJUBA promotes the migration and invasion of esophageal squamous cell carcinoma cells through upregulation of MMP10 and MMP13 expression

Shi, Xuejiao; Chen, Zhaoli; Hu, Xueda; Luo, Mei; Sun, Zengmiao; Li, Jiagen; Shi, Susheng; Feng, Xiaoli; Zhou, Chengcheng; Li, Zitong; Yang, Wenhui; Li, Yuan; Wang, Pan; Zhou, Fang; Gao, Yibo

doi:10.18632/oncotarget.9239

Cited by 38 publications

(57 citation statements)

References 38 publications

(42 reference statements)

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“…LIMD1 functions as a tumor suppressor and is frequently inactivated in lung cancer. In contrast, Shi et al reported AJUBA promotes migration and invasion of esophageal squamous cell carcinoma cells through upregulating MMP10 and MMP13 . Furthermore, influence of AJUBA proteins on EMT is also complicated and dynamic.…”

Section: Discussionmentioning

confidence: 94%

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Gui

Zheng

et al. 2017

The Prostate

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Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR). We elucidated the role of miR-193a-3p and its downstream target gene in PCa cell migration using biochemical approaches. Results We identified a subset of differentially expressed miRNAs in C4-2B cells compared to LNCaP cells. Computational analysis shows that the targets of upregulated miRNAs are significantly associated with downregulated protein-coding mRNAs in C4-2B cells. Gene Ontology analysis further reveals that these downregulated mRNAs are significantly enriched in cell-cell adhesion functions. Downregulation of these miRNA-targeted genes may change PCa cell motility resulting in the acquisition of metastatic potential. We then focus on miR-193a-3p and demonstrate overexpression of miR-193a-3p increases cell migration through downregulating its target AJUBA. AJUBA is a LIM domain protein and contributes to the formation and stability of cadherin-mediated cell-cell adhesion. Loss of AJUBA enhances PCa migration and downregulation of AJUBA expression is observed in metastatic PCa tumors. Conclusions Our results suggest a novel AR/miR-193a-3p/AJUBA pathway implicated in PCa progression. MiR-193a-3p is a potential therapeutic target for metastatic PCa.

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Section: Discussionmentioning

confidence: 94%

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Gui

Zheng

et al. 2017

The Prostate

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“…More recently, another study showed that the AJUBA level was significantly higher in ESCC tissues compared with matched adjacent tissues. AJUBA functions as an oncogenic gene in both in vitro and in vivo experiments 42 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

Huang

et al. 2017

Sci Rep

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Oesophageal carcinoma is the fourth leading cause of cancer-related death in China, and more than 90% of these tumours are oesophageal squamous cell carcinoma (ESCC). Although several ESCC genomic sequencing studies have identified mutated somatic genes, the number of samples in each study was relatively small, and the molecular basis of ESCC has not been fully elucidated. Here, we performed an integrated analysis of 490 tumours by combining the genomic data from 7 previous ESCC projects. We identified 18 significantly mutated genes (SMGs). PTEN, DCDC1 and CUL3 were first reported as SMGs in ESCC. Notably, the AJUBA mutations and mutational signature4 were significantly correlated with a poorer survival in patients with ESCC. Hierarchical clustering analysis of the copy number alteration (CNA) of cancer gene census (CGC) genes in ESCC patients revealed three subtypes, and subtype3 exhibited more CNAs and marked for worse prognosis compared with subtype2. Moreover, database annotation suggested that two significantly differential CNA genes (PIK3CA and FBXW7) between subtype3 and subtype2 may serve as therapeutic drug targets. This study has extended our knowledge of the genetic basis of ESCC and shed some light into the clinical relevance, which would help improve the therapy and prognosis of ESCC patients.

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“…We further validated those genes identified by mass spectrum that have also been reported to be involved in metastasis and invasion (15)(16)(17)(18) by quantitative RT-PCR and Western blotting assays. mRNA levels of Wnt7a, MMP1, MMP10, and S100A8 significantly increased in 5637 HMI compared with 5637 NMI cells ( Fig.…”

Section: Identification Of Dysregulated Proteins In 5637 Hmi Cells Comentioning

confidence: 92%

Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p

Huang

Zhu

Gao

et al. 2018

Journal of Biological Chemistry

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Once urinary bladder cancer (UBC) develops into muscle-invasive bladder cancer, its mortality rate increases dramatically. However, the molecular mechanisms of UBC invasion and metastasis remain largely unknown. Herein, using 5637 UBC cells, we generated two sublines with low (5637 NMI) and high (5637 HMI) invasive capabilities. Mass spectrum analyses revealed that the Wnt family protein Wnt7a is more highly expressed in 5637 HMI cells than in 5637 NMI cells. We also found that increased Wnt7a expression is associated with UBC metastasis and predicted worse clinical outcome in UBC patients. Wnt7a depletion in 5637 HMI and T24 cells reduced UBC cell invasion and decreased levels of active β-catenin and its downstream target genes involved in the epithelial-to-mesenchymal transition (EMT) and extracellular matrix (ECM) degradation. Consistently, treating 5637 NMI and J82 cells with recombinant Wnt7a induced cell invasion, EMT, and expression of ECM degradation-associated genes. Moreover, TOP/FOPflash luciferase assays indicated that Wnt7a activated canonical β-catenin signaling in UBC cells, and increased Wnt7a expression was associated with nuclear β-catenin in UBC samples. Wnt7a ablation suppressed matrix metalloproteinase 10 (MMP10) expression, and Wnt7a overexpression increased promoter activity through two TCF/LEF promoter sites, confirming that Wnt7a-mediated MMP10 activation is mediated by the canonical Wnt/β-catenin pathway. Of note, the microRNA miR-370-3p directly repressed Wnt7a expression and thereby suppressed UBC cell invasion, which was partially restored by Wnt7a overexpression. Our results have identified an miR-370-3p/Wnt7a axis that controls UBC invasion through canonical Wnt/β-catenin signaling, which may offer prognostic and therapeutic opportunities.

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AJUBA promotes the migration and invasion of esophageal squamous cell carcinoma cells through upregulation of MMP10 and MMP13 expression

Cited by 38 publications

References 38 publications

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Androgen receptor‐regulated miRNA‐193a‐3p targets AJUBA to promote prostate cancer cell migration

Comprehensive genomic analysis of Oesophageal Squamous Cell Carcinoma reveals clinical relevance

Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p

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