Autocrine motility factor secreted by HeLa cells inhibits the growth of many cancer cells by regulating AKT/ERK signaling
Autor: | Nam Ho Jeoung, Hee Sung Park |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Autocrine Motility Factor MAP Kinase Signaling System Biophysics Down-Regulation Apoptosis Biochemistry HeLa 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Neoplasms Humans Molecular Biology Protein kinase B Cell Proliferation biology Chemistry Glucose-6-Phosphate Isomerase Cell Biology biology.organism_classification Recombinant Proteins Cell biology Hep G2 030104 developmental biology 030220 oncology & carcinogenesis Culture Media Conditioned Cancer cell Signal transduction Growth inhibition Proto-Oncogene Proteins c-akt HeLa Cells |
Zdroj: | Biochemical and biophysical research communications. 525(3) |
ISSN: | 1090-2104 |
Popis: | In cell competition, a secreted death signal can determine cell fate. However, the nature of such a signal remains unclear. In this study, conditioned medium from HeLa cells (HeLa CM) inhibited growth of A549 and MCF-7 cells. Through HeLa CM fractionation, glucose 6-phosphate isomerase/autocrine motility factor (GPI/AMF) was identified as the main growth inhibitor. Previously, AMF was known for its mitogenic, motogenic, and differentiation functions and was implicated in tumor progression and metastasis. HeLa CM lost its growth inhibitory property after treatment with erythrose-4-phosphate (E4P) or anti-GPI antibody. Purified HeLa recombinant AMF (rAMF) proteins inhibited the growth of A549, MDA-MB-232, MCF-7, AsPC-1, DU145, Hep-2, Hep G2, and HT-29 cells. However, growth of HL-60, SKOV3, U-87 MG, SNU-484, U-87 MG, and 3T3-L1 cells was little affected. In a Transwell assay, HeLa rAMF effectively reduced A549 cell migration and invasion. HeLa rAMF effectively induced apoptosis in A549 cells, apparently by reducing the levels of Bcl-2, GPI, and poly(ADP-ribose) polymerase (PARP)14 and activating caspase-3 and p53. HeLa rAMF antagonized HER2 and the AMF receptor (AMFR or GP78) in relation to the AKT/EKT signaling pathway. These results suggest that HeLa AMF could act as a diffusible death signal that could induce cancer cell–selective growth inhibition and apoptosis. |
Databáze: | OpenAIRE |
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