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Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1a, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.

Cobalt-doped cryptomelane-type manganese oxide (K-OMS-2) microwires have been successfully synthesized and characterized. Their catalytic activity was tested in an oxidation reaction with benzyl alcohol as the substrate, and the cobalt-doped OMS-2 materials showed 100% selectivity toward benzyl aldehyde with a conversion of 55%. The cobalt-doped OMS-2 materials were also investigated as a desulfurization sorbent in a fixed bed reactor at 250 °C where high sulfur sorption capacities (49.4 g of sulfur/100 g of sorbent) were observed. Here, structure-controlled synthesis was performed using a facile one-step microwave-assisted hydrothermal method (MWHY) associated with a rapid temperature ramping (200 °C/min). The structural effects induced by the compositional control of transition metal dopants on the cryptomelane (space group I4/m) body centered tetragonal structure were identified with X-ray diffraction (XRD) and transmission electron microscopy (TEM). The XRD and TEM results showed that the systematic variance of the cobalt content was accompanied by a stepwise lattice expansion of the (110) plane from 6.70 to 7.43 Å. The XRD, high resolution TEM (HRTEM)/TEM, Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) data suggested that the as-synthesized cobalt-doped OMS-2 materials were also crystalline with no segregated metal oxide impurities. The uniform morphology of the metal-doped OMS-2 materials was observed by the field-emission scanning electron microscopy (FESEM), whereas energy-dispersive X-ray (EDX) analysis confirmed the successful incorporation of metal dopant into the OMS-2 structure. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) showed a higher degree of doping (Co/Mn = ∼0.26) associated with the MWHY method over conventional methods. On the other hand, TGA demonstrated that the as-synthesized materials were more thermally unstable than their undoped counterparts. The observed structural and chemical characteristics upon doping with some metal cations were explained by the Jahn–Teller distortion.

Correction to: Oncogene (2018) 37, 1062–1074; doi: 10.1038/onc.2017.368; published online 6 November 2017 This article was originally published under NPG's License to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.