title: Inhibition of autophagy impairs tumor cell invasion in an organotypic model.
abstract: Autophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. It contributes to energy and organelle homeostasis and the preservation of proteome and genome integrity. Although a role in cancer is unquestionable, there are conflicting reports that autophagy can be both oncogenic and tumor suppressive, perhaps indicating that autophagy has different roles at different stages of tumor development. In this report, we address the role of autophagy in a critical stage of cancer progression-tumor cell invasion. Using a glioma cell line containing an inducible shRNA that targets the essential autophagy gene Atg12, we show that autophagy inhibition does not affect cell viability, proliferation or migration but significantly reduces cellular invasion in a 3D organotypic model. These data indicate that autophagy may play a critical role in the benign to malignant transition that is also central to the initiation of metastasis.
authors.affiliation: Beatson Institute for Cancer Research, Glasgow, UK.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Macintosh
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Thorburn
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.forename: Andrew
authors.initials: A
authors.lastname: Thorburn
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001343:Autophagy; D000071192:Autophagy-Related Protein 12; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C491971:Atg12 protein, mouse; D000071192:Autophagy-Related Protein 12; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D011506:Proteins; D034741:RNA, Small Interfering