Biology Reference
In-Depth Information
CHAPTER FIFTEEN
The Role of
-Arrestins in Cancer
b
Philip Michael Sobolesky, Omar Moussa
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South
Carolina, USA
Contents
1.
Introduction
396
2.
ARRBs and Cancer-Associated Cell Phenotypes
397
2.1
Cell proliferation
397
2.2
Cell migration and invasion
398
2.3
Apoptosis and survival
399
3.
The Role of ARRBs in Cancer
400
3.1
Breast cancer
400
3.2
Colorectal cancer
402
3.3
Lung cancer
402
3.4
Bladder cancer
403
3.5
Hematological malignancies
404
3.6
Prostate cancer
405
3.7
Pancreatic cancer
405
3.8
Glioblastoma
406
4.
Conclusions
407
Acknowledgments
407
References
407
Abstract
Beyond their well-characterized roles in G protein-coupled receptor desensitization and
trafficking, b-arrestins (ARRBs) have been implicated in the regulation of several basic
cellular functions, including cell cycle regulation, cell migration, and apoptotic signaling.
Nowhere are the data supporting a physiologically relevant role for these arrestin-
mediated responses stronger than in cancer.
, ARRBs regulate cell proliferation,
promote migration, and transmit anti-apoptotic survival signals by scaffolding cytosolic
signaling protein networks and even translocating to the nucleus to directly regulate
gene expression. In animal models, ARRB expression affects tumor initiation time,
growth rate, vascularization, survival under hypoxic conditions, invasiveness, and met-
astatic potential. Studies in human cancer patients have demonstrated that dys-
regulation of ARRB expression, localization, or phosphorylation is associated with
more aggressive cancer phenotypes and poorer outcomes in malignancies involving
In vitro
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