Sreekumar Lab

Adaptive Glycan Remodeling in Cancer Progression

WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis


Journal article


Amulya Sreekumar, Michael J. Toneff, Eajer Toh, Kevin Roarty, Chad J. Creighton, George K. Belka, Dong-Kee Lee, Jianming Xu, Lewis A. Chodosh, JoAnne S. Richards, Jeffrey M. Rosen
Developmental Cell, vol. 43, Elsevier BV, 2017 Nov, pp. 436–448.e6


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APA   Click to copy
Sreekumar, A., Toneff, M. J., Toh, E., Roarty, K., Creighton, C. J., Belka, G. K., … Rosen, J. M. (2017). WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis. Developmental Cell, 43, 436–448.e6. https://doi.org/10.1016/j.devcel.2017.10.007


Chicago/Turabian   Click to copy
Sreekumar, Amulya, Michael J. Toneff, Eajer Toh, Kevin Roarty, Chad J. Creighton, George K. Belka, Dong-Kee Lee, et al. “WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis.” Developmental Cell 43 (November 2017): 436–448.e6.


MLA   Click to copy
Sreekumar, Amulya, et al. “WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis.” Developmental Cell, vol. 43, Elsevier BV, Nov. 2017, pp. 436–48.e6, doi:10.1016/j.devcel.2017.10.007.


BibTeX   Click to copy

@article{sreekumar2017a,
  title = {WNT-Mediated Regulation of FOXO1 Constitutes a Critical Axis Maintaining Pubertal Mammary Stem Cell Homeostasis},
  year = {2017},
  month = nov,
  journal = {Developmental Cell},
  pages = {436–448.e6},
  publisher = {Elsevier BV},
  volume = {43},
  doi = {10.1016/j.devcel.2017.10.007},
  author = {Sreekumar, Amulya and Toneff, Michael J. and Toh, Eajer and Roarty, Kevin and Creighton, Chad J. and Belka, George K. and Lee, Dong-Kee and Xu, Jianming and Chodosh, Lewis A. and Richards, JoAnne S. and Rosen, Jeffrey M.},
  month_numeric = {11}
}

Abstract

Summary Puberty is characterized by dynamic tissue remodeling in the mammary gland involving ductal elongation, resolution into the mature epithelial bilayer, and lumen formation. To decipher the cellular mechanisms underlying these processes, we studied the fate of putative stem cells, termed cap cells, present in terminal end buds of pubertal mice. Employing a p63CreERT2-based lineage-tracing strategy, we identified a unipotent fate for proliferative cap cells that only generated cells with basal features. Furthermore, we observed that dislocated ‘cap-in-body’ cells underwent apoptosis, which aided lumen formation during ductal development. Basal lineage-specific profiling and genetic loss-of-function experiments revealed a critical role for FOXO transcription factors in mediating these proliferative versus apoptotic fates. Importantly, these studies revealed a mode of WNT signaling-mediated FOXO1 inhibition, potentially mediated through AKT. Together, these data suggest that the WNT pathway confers proliferative and survival advantages on cap cells via regulation of FOXO1 localization.