Abl kinases can function as suppressors of tumor progression and metastasis

Melissa A. Marchal; Devon L. Moose; Afshin Varzavand; Nicole E. Jordan; Destiney Taylor; Munir R. Tanas; James A. Brown; Michael D. Henry; Christopher S. Stipp

doi:10.3389/fonc.2023.1241056

Back

Abl kinases can function as suppressors of tumor progression and metastasis

Journal article

Open access

Peer reviewed

Abl kinases can function as suppressors of tumor progression and metastasis

Melissa A. Marchal, Devon L. Moose, Afshin Varzavand, Nicole E. Jordan, Destiney Taylor, Munir R. Tanas, James A. Brown, Michael D. Henry and Christopher S. Stipp

Frontiers in oncology, Vol.13, 1241056

09/01/2023

DOI: 10.3389/fonc.2023.1241056

PMCID: PMC10514900

PMID: 37746268

Files and links (1)

url

https://doi.org/10.3389/fonc.2023.1241056View

Published (Version of record) Open Access

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. 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.

Metastasis

Prostate Cancer

ABL1

ABL2

AKT

cell motility

Details

Title: Subtitle: Abl kinases can function as suppressors of tumor progression and metastasis
Creators: Melissa A. Marchal - Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United States
Devon L. Moose - University of Iowa
Afshin Varzavand - University of Iowa
Nicole E. Jordan - Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United States
Destiney Taylor - Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United States
Munir R. Tanas - University of Iowa
James A. Brown - University of Iowa
Michael D. Henry - University of Iowa
Christopher S. Stipp - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in oncology, Vol.13, 1241056
DOI: 10.3389/fonc.2023.1241056
PMID: 37746268
PMCID: PMC10514900
NLM abbreviation: Front Oncol
eISSN: 2234-943X
Publisher: Frontiers Media S.A
Language: English
Date published: 09/01/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Dermatology; Molecular Physiology and Biophysics; Pathology; Biology; Urology
Record Identifier: 9984463060302771

Metrics

73 Record Views

1 Times Cited - Web of Science