RT Journal Article
SR Electronic
T1 TET2-mediated epigenetic reprogramming of breast cancer cells impairs lysosome biogenesis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101283
DO 10.26508/lsa.202101283
VO 5
IS 7
A1 Audrey Laurent
A1 Thierry Madigou
A1 Maud Bizot
A1 Marion Turpin
A1 Gaëlle Palierne
A1 Elise Mahé
A1 Sarah Guimard
A1 Raphaël Métivier
A1 Stéphane Avner
A1 Christine Le Péron
A1 Gilles Salbert
YR 2022
UL https://www.life-science-alliance.org/content/5/7/e202101283.abstract
AB Methylation and demethylation of cytosines in DNA are believed to act as keystones of cell-specific gene expression by controlling the chromatin structure and accessibility to transcription factors. Cancer cells have their own transcriptional programs, and we sought to alter such a cancer-specific program by enforcing expression of the catalytic domain (CD) of the methylcytosine dioxygenase TET2 in breast cancer cells. The TET2 CD decreased the tumorigenic potential of cancer cells through both activation and repression of a repertoire of genes that, interestingly, differed in part from the one observed upon treatment with the hypomethylating agent decitabine. In addition to promoting the establishment of an antiviral state, TET2 activated 5mC turnover at thousands of MYC-binding motifs and down-regulated a panel of known MYC-repressed genes involved in lysosome biogenesis and function. Thus, an extensive cross-talk between TET2 and the oncogenic transcription factor MYC establishes a lysosomal storage disease–like state that contributes to an exacerbated sensitivity to autophagy inducers.