Dataset Information

Downregulation of C-Terminal Tensin-Like Protein (CTEN) Suppresses Prostate Cell Proliferation and Contributes to Acinar Morphogenesis.

ABSTRACT: C-terminal tensin-like protein (CTEN) is a member of tensin family, which is crucial for the assembly of cell-matrix adhesome. Unlike other tensins, CTEN is selectively expressed only in a few tissues such as the prostate. However, the biological relevance of CTEN in normal prostate is poorly understood. In this study, we revealed that CTEN is selectively expressed in the prostate epithelial cells and enriched in the basal compartment. Knockdown of CTEN in RWPE-1 cells suppresses cell proliferation and results in G1/S cell cycle arrest as well as the accumulation of cyclin-dependent kinase (CDK) inhibitors, p21 and p27. Moreover, the expression of CTEN is decreased during acinar morphogenesis using Matrigel-based three-dimensional (3D) culture. In the course of acinar formation, induction of CTEN reactivates focal adhesion kinase (FAK) Y397 phosphorylation and disrupts the acini structure. This study, to our knowledge, is the first report demonstrating that downregulation of CTEN is required for luminal differentiation and acinar formation.

SUBMITTER: Wu WM

PROVIDER: S-EPMC6214133 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Downregulation of C-Terminal Tensin-Like Protein (CTEN) Suppresses Prostate Cell Proliferation and Contributes to Acinar Morphogenesis.

Wu Wei-Ming WM Liao Yi-Chun YC

International journal of molecular sciences 20181016 10

C-terminal tensin-like protein (CTEN) is a member of tensin family, which is crucial for the assembly of cell-matrix adhesome. Unlike other tensins, CTEN is selectively expressed only in a few tissues such as the prostate. However, the biological relevance of CTEN in normal prostate is poorly understood. In this study, we revealed that CTEN is selectively expressed in the prostate epithelial cells and enriched in the basal compartment. Knockdown of CTEN in RWPE-1 cells suppresses cell proliferat ...[more]

PMID: 30332774

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Project description:Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expression in normal mammary epithelial cells to gain insight into how LOXL2 mediates cancer progression.LOXL2 was expressed in MCF10A normal human mammary epithelial cells. The 3D acinar morphogenesis of these cells was assessed, as well as the ability of the cells to form branching structures on extracellular matrix (ECM)-coated surfaces. Transwell-invasion assays were used to assess the invasive properties of the cells. Clinically relevant inhibitors of ErbB2, lapatinib and Herceptin (traztuzumab), were used to investigate the role of ErbB2 signaling in this model. A retrospective study on a previously published breast cancer patient dataset was carried out by using Disease Specific Genomic Analysis (DSGA) to investigate the correlation of LOXL2 mRNA expression level with metastasis and survival of ErbB2-positive breast cancer patients.Fluorescence staining of the acini revealed increased proliferation, decreased apoptosis, and disrupted polarity, leading to abnormal lumen formation in response to LOXL2 expression in MCF10A cells. When plated onto ECM, the LOXL2-expressing cells formed branching structures and displayed increased invasion. We noted that LOXL2 induced ErbB2 activation through reactive oxygen species (ROS) production, and ErbB2 inhibition by using Herceptin or lapatinib abrogated the effects of LOXL2 on MCF10A cells. Finally, we found LOXL2 expression to be correlated with decreased overall survival and metastasis-free survival in breast cancer patients with ErbB2-positive tumors.These findings suggest that LOXL2 expression in normal epithelial cells can induce abnormal changes that resemble oncogenic transformation and cancer progression, and that these effects are driven by LOXL2-mediated activation of ErbB2. LOXL2 may also be a beneficial marker for breast cancer patients that could benefit most from anti-ErbB2 therapy.

Dataset Information

Downregulation of C-Terminal Tensin-Like Protein (CTEN) Suppresses Prostate Cell Proliferation and Contributes to Acinar Morphogenesis.

Publications

Downregulation of C-Terminal Tensin-Like Protein (CTEN) Suppresses Prostate Cell Proliferation and Contributes to Acinar Morphogenesis.

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