Metabolic Reprogramming Promotes Neural Crest Migration Via Yap/Tead Signaling

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2020 Apr 4

PMID 32243782

Citations 80

Authors

Debadrita Bhattacharya

Ana Paula Azambuja

Marcos Simoes-Costa

Affiliations

Soon will be listed here.

Abstract

The Warburg effect is one of the metabolic hallmarks of cancer cells, characterized by enhanced glycolysis even under aerobic conditions. This physiological adaptation is associated with metastasis , but we still have a superficial understanding of how it affects cellular processes during embryonic development. Here we report that the neural crest, a migratory stem cell population in vertebrate embryos, undergoes an extensive metabolic remodeling to engage in aerobic glycolysis prior to delamination. This increase in glycolytic flux promotes Yap/Tead signaling, which activates the expression of a set of transcription factors to drive epithelial-to-mesenchymal transition. Our results demonstrate how shifts in carbon metabolism can trigger the gene regulatory circuits that control complex cell behaviors. These findings support the hypothesis that the Warburg effect is a precisely regulated developmental mechanism that is anomalously reactivated during tumorigenesis and metastasis.

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References

Ramirez F, Ryan D, Gruning B, Bhardwaj V, Kilpert F, Richter A . deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016; 44(W1):W160-5. PMC: 4987876. DOI: 10.1093/nar/gkw257. View

Gabbay-Benziv R, Reece E, Wang F, Yang P . Birth defects in pregestational diabetes: Defect range, glycemic threshold and pathogenesis. World J Diabetes. 2015; 6(3):481-8. PMC: 4398903. DOI: 10.4239/wjd.v6.i3.481. View

BARBAN S, SCHULZE H . The effects of 2-deoxyglucose on the growth and metabolism of cultured human cells. J Biol Chem. 1961; 236:1887-90. View

Cha Y, Han M, Cha H, Zoldan J, Burkart A, Jung J . Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis. Nat Cell Biol. 2017; 19(5):445-456. PMC: 5545746. DOI: 10.1038/ncb3517. View

Bailey T, Boden M, Buske F, Frith M, Grant C, Clementi L . MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009; 37(Web Server issue):W202-8. PMC: 2703892. DOI: 10.1093/nar/gkp335. View

Kaufman C, Mosimann C, Fan Z, Yang S, Thomas A, Ablain J . A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science. 2016; 351(6272):aad2197. PMC: 4868069. DOI: 10.1126/science.aad2197. View

Tinevez J, Perry N, Schindelin J, Hoopes G, Reynolds G, Laplantine E . TrackMate: An open and extensible platform for single-particle tracking. Methods. 2016; 115:80-90. DOI: 10.1016/j.ymeth.2016.09.016. View

Dooley C, Wali N, Sealy I, White R, Stemple D, Collins J . The gene regulatory basis of genetic compensation during neural crest induction. PLoS Genet. 2019; 15(6):e1008213. PMC: 6594659. DOI: 10.1371/journal.pgen.1008213. View

Uchikawa M, Ishida Y, Takemoto T, Kamachi Y, Kondoh H . Functional analysis of chicken Sox2 enhancers highlights an array of diverse regulatory elements that are conserved in mammals. Dev Cell. 2003; 4(4):509-19. DOI: 10.1016/s1534-5807(03)00088-1. View

10.

Chapman S, Collignon J, Schoenwolf G, Lumsden A . Improved method for chick whole-embryo culture using a filter paper carrier. Dev Dyn. 2001; 220(3):284-9. DOI: 10.1002/1097-0177(20010301)220:3<284::AID-DVDY1102>3.0.CO;2-5. View

11.

Chavez A, Scheiman J, Vora S, Pruitt B, Tuttle M, Iyer E . Highly efficient Cas9-mediated transcriptional programming. Nat Methods. 2015; 12(4):326-8. PMC: 4393883. DOI: 10.1038/nmeth.3312. View

12.

Mita M, Ito M, Harada K, Sugawara I, Ueda H, Tsuboi T . Green Fluorescent Protein-Based Glucose Indicators Report Glucose Dynamics in Living Cells. Anal Chem. 2019; 91(7):4821-4830. DOI: 10.1021/acs.analchem.9b00447. View

13.

Skene P, Henikoff S . An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017; 6. PMC: 5310842. DOI: 10.7554/eLife.21856. View

14.

Acloque H, Adams M, Fishwick K, Bronner-Fraser M, Nieto M . Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009; 119(6):1438-49. PMC: 2689100. DOI: 10.1172/JCI38019. View

15.

Hsu P, Sabatini D . Cancer cell metabolism: Warburg and beyond. Cell. 2008; 134(5):703-7. DOI: 10.1016/j.cell.2008.08.021. View

16.

Hamburger V, HAMILTON H . A series of normal stages in the development of the chick embryo. J Morphol. 2014; 88(1):49-92. View

17.

Epstein T, Gatenby R, Brown J . The Warburg effect as an adaptation of cancer cells to rapid fluctuations in energy demand. PLoS One. 2017; 12(9):e0185085. PMC: 5602667. DOI: 10.1371/journal.pone.0185085. View

18.

Moussaieff A, Rouleau M, Kitsberg D, Cohen M, Levy G, Barasch D . Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metab. 2015; 21(3):392-402. DOI: 10.1016/j.cmet.2015.02.002. View

19.

Wang C, Bajikar S, Jamal L, Atkins K, Janes K . A time- and matrix-dependent TGFBR3-JUND-KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies. Nat Cell Biol. 2014; 16(4):345-56. PMC: 4035356. DOI: 10.1038/ncb2930. View

20.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View