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

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 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 orthotopic model, and tumor cell motility, 3D growth, and signaling was studied .

Results: Reduced Abl family kinase expression resulted in a highly aggressive, metastatic phenotype that was associated with AKT pathway activation, increased growth on 3D collagen matrix, and enhanced cell motility . 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 , and tumor progression and metastasis .