Abl kinases can function as suppressors of tumor progression and metastasis
IntroductionAbl 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 an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1241056/full |
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| author | Melissa A. Marchal Devon L. Moose Afshin Varzavand Nicole E. Jordan Destiney Taylor Munir R. Tanas Munir R. Tanas James A. Brown James A. Brown Michael D. Henry Michael D. Henry Christopher S. Stipp Christopher S. Stipp |
| author_facet | Melissa A. Marchal Devon L. Moose Afshin Varzavand Nicole E. Jordan Destiney Taylor Munir R. Tanas Munir R. Tanas James A. Brown James A. Brown Michael D. Henry Michael D. Henry Christopher S. Stipp Christopher S. Stipp |
| author_sort | Melissa A. Marchal |
| collection | DOAJ |
| description | IntroductionAbl 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.MethodsTo 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.ResultsReduced 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.ConclusionsCollectively, our data reveal that Abl family kinases can function to suppress malignant cell phenotypes in vitro, and tumor progression and metastasis in vivo. |
| first_indexed | 2024-03-12T01:52:09Z |
| format | Article |
| id | doaj.art-3f74f3b22e7d4202910ff27fb642931d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T01:52:09Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3f74f3b22e7d4202910ff27fb642931d2023-09-08T10:31:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-09-011310.3389/fonc.2023.12410561241056Abl kinases can function as suppressors of tumor progression and metastasisMelissa A. Marchal0Devon L. Moose1Afshin Varzavand2Nicole E. Jordan3Destiney Taylor4Munir R. Tanas5Munir R. Tanas6James A. Brown7James A. Brown8Michael D. Henry9Michael D. Henry10Christopher S. Stipp11Christopher S. Stipp12Department of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United StatesDepartment of Molecular Physiology & Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesDepartment of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United StatesDepartment of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United StatesDepartment of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United StatesDepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesHolden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesHolden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesDepartment of Urology, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesDepartment of Molecular Physiology & Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesHolden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesDepartment of Biology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, United StatesHolden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesIntroductionAbl 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.MethodsTo 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.ResultsReduced 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.ConclusionsCollectively, our data reveal that Abl family kinases can function to suppress malignant cell phenotypes in vitro, and tumor progression and metastasis in vivo.https://www.frontiersin.org/articles/10.3389/fonc.2023.1241056/fullABL1ABL2prostate cancermetastasiscell motilityAKT |
| spellingShingle | Melissa A. Marchal Devon L. Moose Afshin Varzavand Nicole E. Jordan Destiney Taylor Munir R. Tanas Munir R. Tanas James A. Brown James A. Brown Michael D. Henry Michael D. Henry Christopher S. Stipp Christopher S. Stipp Abl kinases can function as suppressors of tumor progression and metastasis Frontiers in Oncology ABL1 ABL2 prostate cancer metastasis cell motility AKT |
| title | Abl kinases can function as suppressors of tumor progression and metastasis |
| title_full | Abl kinases can function as suppressors of tumor progression and metastasis |
| title_fullStr | Abl kinases can function as suppressors of tumor progression and metastasis |
| title_full_unstemmed | Abl kinases can function as suppressors of tumor progression and metastasis |
| title_short | Abl kinases can function as suppressors of tumor progression and metastasis |
| title_sort | abl kinases can function as suppressors of tumor progression and metastasis |
| topic | ABL1 ABL2 prostate cancer metastasis cell motility AKT |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1241056/full |
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