title: c-Myc-Dependent Cell Competition in Human Cancer Cells.
abstract: Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Thaltej, Ahmedabad, 380054, Gujarat, India.
authors.forename: Manish S
authors.identifier: 0000-0002-2450-0662
authors.initials: MS
authors.lastname: Patel
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Thaltej, Ahmedabad, 380054, Gujarat, India.
authors.forename: Heta S
authors.initials: HS
authors.lastname: Shah
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Thaltej, Ahmedabad, 380054, Gujarat, India.|Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Ahmedabad, 380054, Gujarat, India.
authors.forename: Neeta
authors.initials: N
authors.lastname: Shrivastava
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D029721:Drosophila Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: CANCER; CELL COMPETITION; JNK; MCF7; c-Myc