title: Silencing the Metallothionein-2A gene induces entosis in adherent MCF-7 breast cancer cells.
abstract: The presence of a live cell cohabiting within another cell has fascinated scientists for many decades. Far from being a spurious event, many have attempted to uncover the molecular mechanism underlying this phenomenon. In this study, we observed anchorage-dependent MCF-7 cells internalizing neighboring epithelial cells (entosis) after siRNA-mediated silencing of the Metallothionein-2A (MT-2A) gene. MTs belong to a family of low-molecular weight proteins, which bind metal ions endogenously and its over-expression has been reported in a variety of cancers that include breast, prostate, and colon. We provide microscopic evidence at light and ultrastructural levels of the occurrence of entosis after altering MT expression in a subpopulation of MCF-7 breast cancer cells by silencing the MT-2A gene. Our results demonstrate that adheren junctions may play important roles in the formation of cell-in-cell cytostructure after MT-2A gene downregulation and the entotic process does not appear to involve genes associated with autophagy. Interiorized cells often underwent lysosomal degradation within the cytoplasmic body of the engulfing cell. It would appear that a subset of breast cancer cells could die via entosis after MT-2A gene silencing.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Lai
authors.forename: Daina
authors.initials: D
authors.lastname: Lim
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Thomas King-Chor
authors.initials: TK
authors.lastname: Leung
authors.forename: George Wai-Cheong
authors.initials: GW
authors.lastname: Yip
authors.forename: Boon-Huat
authors.initials: BH
authors.lastname: Bay
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D057691:Entosis / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014410:Tumor Stem Cell Assay
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D008668:Metallothionein