LIM-homeobox transcription factor 1, alpha (LMX1A) inhibits tumourigenesis, epithelial–mesenchymal transition and stem-like properties of epithelial ovarian cancer

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

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Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition

10.21203/rs.3.rs-86051/v2 ◽

2020 ◽

Author(s):

Jiani Yang ◽

Jun Ma ◽

Yue Jin ◽

Shanshan Cheng ◽

Shan Huang ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Stratification ◽

Epithelial Ovarian Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Epithelial Mesenchymal Transition ◽

Ca 125 ◽

Mesenchymal Transition ◽

Cox Regression Analysis ◽

Significant Difference

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

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IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer

OncoTargets and Therapy ◽

10.2147/ott.s147855 ◽

2018 ◽

Vol Volume 11 ◽

pp. 2037-2050 ◽

Cited By ~ 10

Author(s):

Yunxia Zhang ◽

Jing Wang ◽

Di Wu ◽

Miao Li ◽

Fengshu Zhao ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Epithelial Ovarian Cancer ◽

Epithelial Mesenchymal Transition ◽

Beta Catenin ◽

Inhibit Tumor Growth ◽

Mesenchymal Transition ◽

Tumor Growth And Metastasis

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Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor

Molecular and Cellular Biology ◽

10.1128/mcb.00297-16 ◽

2016 ◽

Vol 37 (5) ◽

Cited By ~ 16

Author(s):

Liza J. Burton ◽

Jodi Dougan ◽

Jasmine Jones ◽

Bethany N. Smith ◽

Diandra Randle ◽

...

Keyword(s):

Transcription Factor ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Cathepsin L ◽

Mesenchymal Cells ◽

Mesenchymal Transition ◽

Ccaat Displacement Protein ◽

Homeobox Transcription Factor ◽

Mcf 7 ◽

E Cadherin

ABSTRACT The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells. There was increased binding of CUX1 to Snail and the E-cadherin promoter in mesenchymal cells compared to epithelial prostate and breast cells. Treatment of mesenchymal cells with the Cat L inhibitor Z-FY-CHO led to nuclear-to-cytoplasmic relocalization of Cat L, decreased binding of CUX1 to Snail and the E-cadherin promoter, reversed EMT, and decreased cell migration/invasion. Overall, our novel data suggest that a positive feedback loop between Snail-nuclear Cat L-CUX1 drives EMT, which can be antagonized by Z-FY-CHO. Therefore, Z-FY-CHO may be an important therapeutic tool to antagonize EMT and cancer progression.

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