Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2

Zhang, Jia Xing; Chen, Zhen Hua; Xu, Yi; Chen, Jie Wei; Weng, Hui; Miao, Yun; Zheng, Zou San; Cui, Chen; Wu, Bing; Li, En Min; Fu, Jianhua; Ye, Sheng; Xie, Dan

doi:10.1158/1078-0432.ccr-16-0414

Cited by 53 publications

(47 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metastasis-promoting function of Id1, MMP-1, integrin alpha6 and PITX2, for example, requires activation of the PI3K/AKT pathway [7, 21–23]. Here, our results showed that p-AKT expression was increased in the highly invasive esophageal cancer sublines and was likely due to downregulation of PTEN.…”

Section: Discussionmentioning

confidence: 57%

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy

Lam

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Metastasis is the most lethal hallmark of esophageal squamous cell carcinoma (ESCC). The aim of the study is to identify key signaling pathways that control metastasis in ESCC. Highly invasive ESCC sublines (designated I3 cells) were established through three rounds of selection of cancer cells invading through matrigel-coated chambers. Gene expression profile of one of the I3 sublines was compared with that of its parental cell line using cDNA microarray analysis. Gene ontology and pathway analyses of the differentially expressed genes (both upregulated and downregulated) indicated that genes associated with cellular movement and the AKT pathway were associated with increased cancer cell invasiveness. Western blot analysis confirmed increased phosphorylated AKT (p-AKT), N-cadherin and decreased E-cadherin expression in the I3 cells. Immunohistochemistry was used to evaluate the clinical significance of p-AKT expression in ESCC, and the results showed higher p-AKT nuclear expression in lymph node metastases when compared with primary carcinoma. Inactivation of the PI3K/AKT pathway with specific inhibitors, or with PTEN overexpression, resulted in reversed cadherin switching and inhibited cancer cell motility. Inhibition of the pathway by treatment with wortmannin markedly suppressed experimental metastasis in nude mice. Our data demonstrated the importance of the PI3K/AKT signaling pathway in ESCC metastasis and support PI3K/AKT as a valid therapeutic target in treatment of metastatic ESCC.

show abstract

Section: Discussionmentioning

confidence: 57%

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy

Lam

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…In contrast a high PITX2 protein expression, suggestive of a low or unmethylated PITX2 gene, is found in colorectal cancer where the WNT/β-Catenin is predominantly activated due to APC mutations [53]. The same has been demonstrated in other tumors with an aberrant WNT/ß-catenin pathway like esophageal squamous cell cancer [54, 55]. …”

Section: Discussionmentioning

confidence: 99%

PITX2andPANCRDNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma

et al. 2016

View full text Add to dashboard Cite

BackgroundSquamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.ResultsPITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010).MethodsQuantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy).ConclusionsPITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.

show abstract

“…Primary antibodies against TRPM7 (1:200 dilutions, Abcam) were used in this study. Detailed procedures of IHC were as described previously (15). The intensity of staining in tumor cells was scored by two pathologists independently.…”

Section: Clinical Patient Cohort and Tissue Specimensmentioning

confidence: 99%

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Zhao

Zhang

Duan

et al. 2018

Molecular Cancer Research

View full text Add to dashboard Cite

Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of and assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation and tumor growth Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease. TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. .

show abstract

Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2

Cited by 53 publications

References 44 publications

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy

Significance of PI3K/AKT signaling pathway in metastasis of esophageal squamous cell carcinoma and its potential as a target for anti-metastasis therapy

PITX2andPANCRDNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma

TRPM7 Regulates AKT/FOXO1–Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma

Contact Info

Product

Resources

About