Macrophage induced ERK-TGF-β1 signaling in MCF7 breast cancer cells result in reversible cancer stem cell plasticity and epithelial mesenchymal transition

Autor:	Priya Kundu, Bhavani S. Shankar
Rok vydání:	2022
Předmět:	Transforming Growth Factor beta1 Mice Epithelial-Mesenchymal Transition Macrophages Neoplasms Biophysics MCF-7 Cells Neoplastic Stem Cells Animals Humans Mice SCID Molecular Biology Biochemistry
Zdroj:	Biochimica et biophysica acta. General subjects. 1866(11)
ISSN:	1872-8006
Popis:	Breast cancer is a heterogenous disease composed of multiple clonal populations and the mechanism by which the tumor microenvironment induces cancer stem cell plasticity is not fully understood.MCF7 breast cancer cells were treated with macrophage conditioned medium (MɸCM). PD98059 and SB431542 were used for ERK and TGF-βR inhibition respectively. Epithelial-mesenchymal transition (EMT) and cancer stem cell markers (CSC) were studied using qRT-PCR and flowcytometry. SCID mice were used for animal experiments.MɸCM- induced ERK/TGF-β1 signaling led to enrichment of CSC and EMT in MCF7 cells and mammospheres. These effects were abrogated by both MEK inhibitor PD98059 (TGF-β1 synthesis) and SB431542 (TGF-β1 signaling). The increase in CSC was both hybrid (ALDH1ERK signaling plays an important role in MɸCM- induced EMT and CSC plasticity which is completely reversible upon withdrawal of signals.Our experimental observations support the semi-independent nature of EMT-stemness connection which is very dynamic and reversible depending on the microenvironment.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d58f91dd33437ff2c5110bef54188d0b https://pubmed.ncbi.nlm.nih.gov/35905921 Zobrazit plný text záznamu Full Text from ScienceDirect