Dataset Information

Abl kinases can function as suppressors of tumor progression and metastasis.

ABSTRACT:

Introduction

Abl family kinases function as proto-oncogenes in various leukemias, and pro-tumor functions have been discovered for Abl kinases in many solid tumors as well. However, a growing body of evidence indicates that Abl kinases can function to suppress tumor cell proliferation and motility and tumor growth in vivo in some settings.

Methods

To investigate the role of Abl kinases in tumor progression, we used RNAi to generate Abl-deficient cells in a model of androgen receptor-indifferent, metastatic prostate cancer. The effect of Abl kinase depletion on tumor progression and metastasis was studied in an in vivo orthotopic model, and tumor cell motility, 3D growth, and signaling was studied in vitro.

Results

Reduced Abl family kinase expression resulted in a highly aggressive, metastatic phenotype in vivo that was associated with AKT pathway activation, increased growth on 3D collagen matrix, and enhanced cell motility in vitro. Inhibiting AKT pathway signaling abolished the increased 3D growth of Abl-deficient cells, while treatment with the Abl kinase inhibitor, imatinib, promoted 3D growth of multiple additional tumor cell types. Moreover, Abl kinase inhibition also promoted soft-agar colony formation by pre-malignant fibroblasts.

Conclusions

Collectively, our data reveal that Abl family kinases can function to suppress malignant cell phenotypes in vitro, and tumor progression and metastasis in vivo.

SUBMITTER: Marchal MA

PROVIDER: S-EPMC10514900 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Abl kinases can function as suppressors of tumor progression and metastasis.

Marchal Melissa A MA Moose Devon L DL Varzavand Afshin A Jordan Nicole E NE Taylor Destiney D Tanas Munir R MR Brown James A JA Henry Michael D MD Stipp Christopher S CS

Frontiers in oncology 20230908

<h4>Introduction</h4>Abl family kinases function as proto-oncogenes in various leukemias, and pro-tumor functions have been discovered for Abl kinases in many solid tumors as well. However, a growing body of evidence indicates that Abl kinases can function to suppress tumor cell proliferation and motility and tumor growth <i>in vivo</i> in some settings.<h4>Methods</h4>To investigate the role of Abl kinases in tumor progression, we used RNAi to generate Abl-deficient cells in a model of androgen ...[more]

PMID: 37746268

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Dataset Information

Abl kinases can function as suppressors of tumor progression and metastasis.

Introduction

Methods

Results

Conclusions

Publications

Abl kinases can function as suppressors of tumor progression and metastasis.

Similar Datasets

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