Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma

Lixing Zhan ¹, Avi Rosenberg , Kenneth C Bergami

⁰Cold Spring Harbor Laboratory, Watson School of Biological Sciences, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.

Cell +

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December 2, 2008

View abstract on PubMed

Summary

Loss of Scribble protein disrupts cell polarity and morphogenesis, promoting mammary tumors in mammals. This protein normally inhibits breast cancer by maintaining cell death and tissue structure.

Area Of Science

Cell Biology
Developmental Biology
Cancer Research

Background

Cell polarity proteins, like Scribble, are crucial for tissue organization.
Their role in mammalian tumorigenesis, particularly breast cancer, remains unclear.
Uncontrolled cell proliferation is a hallmark of neoplasia.

Purpose Of The Study

To investigate the function of Scribble in mammalian mammary epithelial cells.
To determine Scribble's role in tumorigenesis and its interaction with oncogenes.
To explore the implications of Scribble deregulation in spontaneous mammary tumors.

Main Methods

Depletion of Scribble in mouse mammary epithelia.
Analysis of cell polarity, 3D morphogenesis, and apoptosis.
Co-expression studies with oncogenes like c-myc.
Examination of Scribble expression in human and mouse mammary tumors.

Main Results

Scribble depletion disrupted mammary epithelial cell polarity and 3D morphogenesis.
Loss of Scribble inhibited apoptosis and induced mammary dysplasia, leading to tumors.
Scribble loss cooperated with c-myc to promote cell transformation and tumor formation by blocking apoptosis.
Mislocalized Scribble also induced cell transformation.
Downregulated and mislocalized Scribble were observed in spontaneous mouse and human mammary tumors.

Conclusions

Scribble acts as a tumor suppressor in breast cancer.
Deregulation of Scribble and cell polarity pathways promotes mammary dysplasia and tumorigenesis.
Disruption of morphogenesis and inhibition of apoptosis are key mechanisms by which Scribble loss drives cancer.

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