C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer

Xiao-Zheng Liu, Anastasiia Rulina, Man Hung Choi, Line Pedersen, Johanna Lepland, Sina T. Takle, Noelly Madeleine, Stacey D’mello Peters, Cara Ellen Wogsland, Sturla Magnus Grøndal, James B. Lorens, Hani Goodarzi, Per E. Lønning, Stian Knappskog, Anders Molven and Nils Halberg ()
Additional contact information
Xiao-Zheng Liu: University of Bergen
Anastasiia Rulina: University of Bergen
Man Hung Choi: University of Bergen
Line Pedersen: University of Bergen
Johanna Lepland: University of Bergen
Sina T. Takle: University of Bergen
Noelly Madeleine: University of Bergen
Stacey D’mello Peters: University of Bergen
Cara Ellen Wogsland: University of Bergen
Sturla Magnus Grøndal: University of Bergen
James B. Lorens: University of Bergen
Hani Goodarzi: University of California San Francisco
Per E. Lønning: University of Bergen
Stian Knappskog: University of Bergen
Anders Molven: University of Bergen
Nils Halberg: University of Bergen

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal breast cancer. Moreover, it is known that obesity promotes stem cell-like properties of breast cancer cells. However, the cancer cell-autonomous mechanisms underlying this correlation are not well defined. Here we demonstrate that obesity-associated tumor formation is driven by cellular adaptation rather than expansion of pre-existing clones within the cancer cell population. While there is no correlation with specific mutations, cellular adaptation to obesity is governed by palmitic acid (PA) and leads to enhanced tumor formation capacity of breast cancer cells. This process is governed epigenetically through increased chromatin occupancy of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPB). Obesity-induced epigenetic activation of C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators including CLDN1 and LCN2. Collectively, our findings demonstrate that obesity drives cellular adaptation to PA drives tumor initiation in the obese setting through activation of a C/EBPB dependent transcriptional network.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27734-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27734-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27734-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().