Dataset Information

EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells

ABSTRACT: Tumors and tumor surrounding tissues produce multiple growth factors that influence tumor cell behavior via different signal transduction pathways. Growth factors like transforming growth factor beta (TGFβ) and epidermal growth factor (EGF) were 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, similarities and differences of their contributions to cancer cell migration and invasion are not fully understood. Here we compared the impact of TGFβ, EGF and the combination of both factors on A549 cells. Both factors stimulated A549 migration to a similar extent but with a different kinetic and the combination had an additive effect. While EGF-induced migration depended on activation of the mitogen-activated protein kinase (MAPK) pathway, this pathway was dispensable for TGFβ-induced migration despite a strong activation by TGFβ. Proteome analysis revealed an overlap in expression patterns of migration-related proteins and associated gene ontology (GO) terms by TGFβ and EGF but 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, EGF was unable to increase invasion of A549 cells on its own and failed to enhance TGFβ-induced invasion. Overall, these data suggest that TGFβ and EGF may partly compensate each other for stimulation of cell migration but abrogation of TGFβ signaling may be more suitable for antagonizing invasion.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Christopher Gerner

LAB HEAD: Christopher Gerner

PROVIDER: PXD023024 | Pride | 2021-04-08

REPOSITORIES: Pride

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EGF Induces Migration Independent of EMT or Invasion in A549 Lung Adenocarcinoma Cells.

Schelch Karin K Vogel Lisa L Schneller Anja A Brankovic Jelena J Mohr Thomas T Mayer Rupert L RL Slany Astrid A Gerner Christopher C Grusch Michael M

Frontiers in cell and developmental biology 20210312

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 ...[more]

PMID: 33777943

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Project description:Laminin-5 gamma-2 (LAMC2) is highly expressed in anaplastic thyroid carcinoma and associated with tumor progression, migration and invasion by modulating signaling of EGFR LAMC2 was highly expressed in ATC samples and cell lines compared to normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed migration, invasion and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells, reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered expression of genes associated with migration, invasion, proliferation and survival. Immunoprecipitation studies showed that LAMC2 was bound to EGFR in ATC cells. Silencing of LAMC2 partially blocked EGF-mediated activation of EGFR and its downstream pathway. Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit gamma-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumour invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC. LAMC2 was highly expressed in ATC samples and cell lines compared to normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed migration, invasion and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells, reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered expression of genes associated with migration, invasion, proliferation and survival. Immunoprecipitation studies showed that LAMC2 was bound to EGFR in ATC cells. Silencing of LAMC2 partially blocked EGF-mediated activation of EGFR and its downstream pathway. LAMC2 was highly expressed in ATC samples and cell lines compared to normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed migration, invasion and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells, reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered expression of genes associated with migration, invasion, proliferation and survival. Immunoprecipitation studies showed that LAMC2 was bound to EGFR in ATC cells. Silencing of LAMC2 partially blocked EGF-mediated activation of EGFR and its downstream pathway. Anaplastic thyroid carcinoma cell lines (HTH83 and TL3) were infected with scrambled shRNA and LAMC2 shRNA and stable clones from each cell line were generated and used for RNA extraction and hybridization on Illumina Microarray. We compared scrambled shRNA stable cells with LAMC2 shRNA stable cells.

			Action	DRS
	A549_cyt_EGF_1_1.mzML	Mzml
	A549_cyt_EGF_1_1.mzid.gz	Mzid
	A549_cyt_EGF_1_1.raw	Raw
	A549_cyt_EGF_1_2.mzML	Mzml
	A549_cyt_EGF_1_2.mzid.gz	Mzid