The Primary Cilium of Adipose Progenitors Is Necessary for Their Differentiation into Cancer-Associated Fibroblasts that Promote Migration of Breast Cancer Cells In Vitro
Open Access
- 8 October 2020
- Vol. 9 (10), 2251
- https://doi.org/10.3390/cells9102251
Abstract
Cancer associated fibroblasts (CAFs) are central elements of the microenvironment that control tumor development. In breast cancer, CAFs can originate from adipose progenitors (APs). We, and others, have shown that the primary cilium, an antenna-shaped organelle, controls several aspects of APs’ biology. We studied the conversion of human APs into CAFs by breast cancer cell lines (BCCs). Deletion of the cilium of APs by a pharmacological inhibitor, or by siRNA, allow us to demonstrate that the cilium is necessary for the differentiation of APs into CAFs. BCCs increase production of TGF-β1 by APs, which is a known inducer of CAFs. Pharmacological inhibition of TGF-β1 signaling in APs prevents their conversion into CAFs. Since we previously showed that deletion of the APs’ cilium inhibits TGF-β1 signaling, we propose that BCCs induce TGF-β1 production in Aps, which binds to the primary cilium of Aps and leads to their differentiation into CAFs. Inhibition of APs conversion into CAFs induces a loss in some of the biological effects of CAFs since deletion of the cilium of APs decreases their effect on the migration of BCCs. This is the first observation of a function of the cilium of APs in their conversion into CAFs, and its consequences on BCCs.This publication has 46 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Small-molecule inhibitors of the AAA+ ATPase motor cytoplasmic dyneinNature, 2012
- Leptin Mediates Tumor–Stromal Interactions That Promote the Invasive Growth of Breast Cancer CellsCancer Research, 2012
- Ciliogenesis: building the cell's antennaNature Reviews Molecular Cell Biology, 2011
- Primary Cilia Are Decreased in Breast Cancer: Analysis of a Collection of Human Breast Cancer Cell Lines and TissuesJournal of Histochemistry & Cytochemistry, 2010
- Primary Cilia Regulate Branching Morphogenesis during Mammary Gland DevelopmentCurrent Biology, 2010
- Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockadeProceedings of the National Academy of Sciences of the United States of America, 2009
- Carcinoma-Associated Fibroblast–Like Differentiation of Human Mesenchymal Stem CellsCancer Research, 2008
- The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cellsJournal of Cell Science, 2007
- An incredible decade for the primary cilium: a look at a once-forgotten organelleAmerican Journal of Physiology-Renal Physiology, 2005