American Association for Cancer Research
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Figure S4 from ADAMDEC1 Maintains a Growth Factor Signaling Loop in Cancer Stem Cells

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journal contribution
posted on 2023-04-03, 21:43 authored by Ana Jimenez-Pascual, James S. Hale, Anja Kordowski, Jamie Pugh, Daniel J. Silver, Defne Bayik, Gustavo Roversi, Tyler J. Alban, Shilpa Rao, Rui Chen, Thomas M. McIntyre, Giorgio Colombo, Giulia Taraboletti, Karl O. Holmberg, Karin Forsberg-Nilsson, Justin D. Lathia, Florian A. Siebzehnrubl

Supplementary Figure S4


Medical Research Council

Tenovus Cancer

Cancer Research UK

Lisa Dean Moseley Foundation

Cleveland Clinic

Case Comprehensive Cancer

Comprehensive Cancer Center



Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (GSC), but how GSCs maintain their stemness is incompletely understood and the subject of intense investigation. Here, we identify a novel signaling loop that induces and maintains GSCs consisting of an atypical metalloproteinase, ADAMDEC1, secreted by GSCs. ADAMDEC1 rapidly solubilizes FGF2 to stimulate FGFR1 expressed on GSCs. FGFR1 signaling induces upregulation of ZEB1 via ERK1/2 that regulates ADAMDEC1 expression through miR-203, creating a positive feedback loop. Genetic or pharmacologic targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signaling axis for GSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM. Cancer stem cells (CSC) drive tumor growth in many cancers including GBM. We identified a novel sheddase, ADAMDEC1, which initiates an FGF autocrine loop to promote stemness in CSCs. This loop can be targeted to reduce GBM growth.This article is highlighted in the In This Issue feature, p. 1469

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