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The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/?-catenin signaling and silenced in common carcinomas.

ABSTRACT: Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (~1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently detected in tumor cell lines, but not in immortalized normal epithelial cells. Aberrant methylation was also frequently detected in multiple primary tumors. CDH11 silencing could be reversed by pharmacologic or genetic demethylation, indicating an epigenetic mechanism. Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/?-catenin and AKT/Rho A signaling, as well as actin stress fiber formation, thus further inhibiting tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal transition and downregulated stem cell markers. Thus, our work identifies CDH11 as a functional tumor suppressor and an important antagonist of Wnt/?-catenin and AKT/Rho A signaling, with frequent epigenetic inactivation in common carcinomas.

SUBMITTER: Li L

PROVIDER: S-EPMC3426851 | biostudies-other | 2012 Aug

REPOSITORIES: biostudies-other

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The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas.

Li L L Ying J J Li H H Zhang Y Y Shu X X Fan Y Y Tan J J Cao Y Y Tsao S W SW Srivastava G G Chan A T C AT Tao Q Q

Oncogene 20111205 34

Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (~1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently de ...[more]

PMID: 22139084

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Project description:Background:The urgent problem in the treatment of breast cancer is the recurrence induced by breast cancer stem cells (CSCs). Understanding the role and molecular mechanism of specific molecules in breast cancer stem cells can provide a theoretical basis for better treatment. TRIP6 is an adapter protein which belongs to the zyxin family of LIM proteins and is important in regulating the functions of CSCs. The present study aims to investigate the effects and mechanism of TRIP6 in breast cancer. Methods:TRIP6 expression in breast cancer cells and tissues were detected by Real-Time PCR, western blot and immunohistochemistry (IHC). MTT assays, colony formation assays, Xenografted tumor model and mammosphere formation assays were performed to investigate the oncogenic functions of TRIP6 in the tumorigenic capability and the tumor-initiating cell-like phenotype of breast cancer cells in vitro and in vivo. Luciferase reporter, subcellular fractionation and immunofluorescence staining assays were performed to determine the underlying mechanism of TRIP6-mediated stemness of breast cancer cells. Results:TRIP6 expression was significantly upregulated in breast cancer, and was closely related to the clinicopathologic characteristics, poor overall survival (OS), relapse-free survival (RFS) and poor prognosis of breast cancer patients. Functional studies revealed that overexpression of TRIP6 significantly enhanced proliferative, tumorigenicity capability and the cancer stem cell-like properties of breast cancer in vitro and in vivo. On the contrary, silencing TRIP6 achieved the opposite results. Notably, we found that TRIP6 promoted Wnt/?-catenin signaling pathway in breast cancer to strengthen the tumor-initiating cell-like phenotype of breast cancer cells. Conclusions:This study indicates that TRIP6 plays an important role in maintaining the stem cell-like characteristics of breast cancer cells, supporting the significance of TRIP6 as a novel potential prognostic biomarker and therapeutic target for diagnosis and treatment of breast cancer.

Dataset Information

The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/?-catenin signaling and silenced in common carcinomas.

Publications

The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas.

Similar Datasets

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