Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Abstract

Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC.

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

“…To elucidate the underlying mechanism of melatonin and its possibility of paclitaxel sensitizer, the current work was performed in X02 cancer stem cells. Herein CXCR4, CD44, CD133, CD90, SOX‐2, and nestin at protein level and nestin, A20, CXCR4 at mRNA level as stem cell markers were highly expressed in X02 cells compared to other cancer cells such as U87, U373, and T98G cells in X02 cells, indicating X02 cells have stem cell property. Furthermore, melatonin disturbed sphere formation and renewal property in a time‐dependent fashion as well as reduced the expression of SOX‐2, CXCR4, nestin, and NANOG in X02 cells, implying inhibitory effect of melatonin on cancer stem cell (CSC) property.…”

CBF1 is clinically prognostic and serves as a target to block cellular invasion and chemoresistance of EMT-like glioblastoma cells

“…Targeting the Notch signalling pathway is an efficient strategy to eradicate CSCs with several promising clinical trials underway (Kahlert et al , 2017). CBF1 is a central signal mediator of the Notch network that has both pathway-activating and -suppressive functions (Bray, 2006).…”

“…Recent developments in cancer research led to the consideration that targeting metabolic networks can be a promising way to effectively target cancer malignancy, including in glioblastoma (Kahlert et al , 2017). In breast cancer, EMT induces glycolytic metabolism (Kondaveeti et al , 2015) and glycolysis is the primary energy pathway used for breast and prostate cancer cell motility (Shiraishi et al , 2015).…”

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

“…Phylogenetically conserved stem cell signaling pathways represent the most accepted anti-CSC targets in various tumors including GBM (Kahlert et al, 2017;Takebe et al, 2015). Interfering with such pathways has been shown to affect MT in GBMs.…”