EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells
Tumors and the tumor microenvironment produce multiple growth factors that influence cancer cell behavior via various signal transduction pathways. Growth factors, like transforming growth factor β (TGFβ) and epidermal growth factor (EGF), have been shown to induce proliferation, migration, and inva...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.634371/full |
| _version_ | 1818576646950617088 |
|---|---|
| author | Karin Schelch Lisa Vogel Anja Schneller Jelena Brankovic Thomas Mohr Rupert L. Mayer Astrid Slany Christopher Gerner Michael Grusch |
| author_facet | Karin Schelch Lisa Vogel Anja Schneller Jelena Brankovic Thomas Mohr Rupert L. Mayer Astrid Slany Christopher Gerner Michael Grusch |
| author_sort | Karin Schelch |
| collection | DOAJ |
| description | Tumors and the tumor microenvironment produce multiple growth factors that influence cancer cell behavior via various signal transduction pathways. Growth factors, like transforming growth factor β (TGFβ) and epidermal growth factor (EGF), have been shown to induce proliferation, migration, and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, the similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of treating A549 lung adenocarcinoma cells with TGFβ, EGF, and both in combination by applying videomicroscopy, functional assays, immunoblotting, real-time PCR, and proteomics. Treatment with both factors stimulated A549 migration to a similar extent, but with different kinetics. The combination had an additive effect. EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway. However, this pathway was dispensable for TGFβ-induced migration, despite a strong activation of this pathway by TGFβ. Proteome analysis (data are available via ProteomeXchange with identifier PXD023024) revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF. Further, only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF, in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, TGFβ treatment significantly increased the invasive capacity of A549 cells, while EGF treatment did not. Moreover, the addition of EGF failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF can partly compensate for each other for stimulation of cell migration, but abrogation of TGFβ signaling may be more suitable to suppress cell invasion. |
| first_indexed | 2024-12-16T06:17:20Z |
| format | Article |
| id | doaj.art-cca4bf5f16334916af72b310b2d5d801 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T06:17:20Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-cca4bf5f16334916af72b310b2d5d8012022-12-21T22:41:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.634371634371EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma CellsKarin Schelch0Lisa Vogel1Anja Schneller2Jelena Brankovic3Thomas Mohr4Rupert L. Mayer5Astrid Slany6Christopher Gerner7Michael Grusch8Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaDepartment of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna, AustriaInstitute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, AustriaTumors and the tumor microenvironment produce multiple growth factors that influence cancer cell behavior via various signal transduction pathways. Growth factors, like transforming growth factor β (TGFβ) and epidermal growth factor (EGF), have been shown to induce proliferation, migration, and invasion in different cell models. Both factors are frequently overexpressed in cancer and will often act in combination. Although both factors are being used as rational targets in clinical oncology, the similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of treating A549 lung adenocarcinoma cells with TGFβ, EGF, and both in combination by applying videomicroscopy, functional assays, immunoblotting, real-time PCR, and proteomics. Treatment with both factors stimulated A549 migration to a similar extent, but with different kinetics. The combination had an additive effect. EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway. However, this pathway was dispensable for TGFβ-induced migration, despite a strong activation of this pathway by TGFβ. Proteome analysis (data are available via ProteomeXchange with identifier PXD023024) revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF. Further, only TGFβ induced the expression of epithelial to mesenchymal transition (EMT)-related proteins like matrix metalloproteinase 2 (MMP2). EGF, in contrast, made no major contribution to EMT marker expression on either the protein or the transcript level. In line with these expression patterns, TGFβ treatment significantly increased the invasive capacity of A549 cells, while EGF treatment did not. Moreover, the addition of EGF failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF can partly compensate for each other for stimulation of cell migration, but abrogation of TGFβ signaling may be more suitable to suppress cell invasion.https://www.frontiersin.org/articles/10.3389/fcell.2021.634371/fullcell migrationEGFTGFβlung cancerepithelial to mesenchymal transition |
| spellingShingle | Karin Schelch Lisa Vogel Anja Schneller Jelena Brankovic Thomas Mohr Rupert L. Mayer Astrid Slany Christopher Gerner Michael Grusch EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells Frontiers in Cell and Developmental Biology cell migration EGF TGFβ lung cancer epithelial to mesenchymal transition |
| title | EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells |
| title_full | EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells |
| title_fullStr | EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells |
| title_full_unstemmed | EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells |
| title_short | EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells |
| title_sort | egf induces migration independent of emt or invasion in a549 lung adenocarcinoma cells |
| topic | cell migration EGF TGFβ lung cancer epithelial to mesenchymal transition |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.634371/full |
| work_keys_str_mv | AT karinschelch egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT lisavogel egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT anjaschneller egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT jelenabrankovic egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT thomasmohr egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT rupertlmayer egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT astridslany egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT christophergerner egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells AT michaelgrusch egfinducesmigrationindependentofemtorinvasionina549lungadenocarcinomacells |