Transcriptomic analysis of effects of cancer cell detachment after treatment with 2-deoxy-D-glucose alone or in co-treatment with metformin

Detachment of cancer cells from tumor, anchorage-independent survival, and maintenance of proliferative capacity upon reattachment are crucial steps in metastases formation. Better understanding of the underlying molecular mechanisms could help to improve targeted cancer therapies. We show reversible detachment of cancer cells using N-glycosylation inhibitors 2-deoxy-D-glucose (2DG) and tunicamycin, with re-attached cells retaining their proliferating capacity. This phenomenon was enhanced by combining with inhibitors of the electron transport chain. Analysis of the detached MDA-MB-231 cells treated with 2DG or 2DG combined with metformin showed ER stress, upregulation of pentose phosphate pathway, stemness, and alterations in genes involved in EMT.