GAS6/AXL Axis Regulates Prostate Cancer Invasion, Proliferation, and Survival in the Bone Marrow Niche

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2010 Feb 4

PMID 20126470

Citations 177

Authors

Yusuke Shiozawa

Elisabeth A Pedersen

Lalit R Patel

Anne M Ziegler

Aaron M Havens

Younghun Jung

Jingcheng Wang

Stephanie Zalucha

Robert D Loberg

Kenneth J Pienta

Russell S Taichman

Affiliations

Soon will be listed here.

Abstract

Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bone marrow. The role of the niche is thought to be the induction and sustenance of HSC dormancy. If metastatic PCa cells occupy a similar or the same ecological niche as HSCs, then it is likely that the initial role of the HSC niche will be to induce dormancy in metastatic cells. In this study, we demonstrate that the binding of PCa to annexin II induces the expression of the growth arrest-specific 6 (GAS6) receptors AXL, Sky, and Mer, which, in the hematopoietic system, induce dormancy. In addition, GAS6 produced by osteoblasts prevents PCa proliferation and protects PCa from chemotherapy-induced apoptosis. Our results suggest that the activation of GAS6 receptors on PCa in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy.

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