RNA epigenetics as a key regulator of cancer metastasis
Although metastasis are responsible for more than 90% of all cancer deaths, limited progress has been made in treating cancers that have spread.
Analyzing data from thousands of cancer patients, the ULB researchers discovered that FTO is produced at lower levels in cancers than in healthy tissues. When they experimentally lowered the levels of FTO in cancer cells grown in plastic dishes or in animal models, they observed that these cells grew and spread faster than control cells. In cancer patients, they discovered a similar pattern in which low FTO levels correlated with more aggressive tumors, metastasis and earlier death. Using a new sequencing technology, which allows to measure m6A within all mRNAs, Prof. Fuks and Dr. Jeschke found that in FTO-low cancer cells m6A is enriched specifically in mRNAs that belong to a program, termed WNT signaling, that promotes metastasis.
As WNT signaling has been found upregulated in many cancers, therapies that aim to block this program have been developed and are currently tested in clinical trials. When the ULB researchers experimented with this new type of therapy, they observed that cancer cells or tumors with lowered FTO levels and enhanced WNT activity were more sensitive to WNT inhibitors. Thus, although FTO-low tumors are more aggressive and deadly, they are better treatable with Wnt inhibitor therapy. The findings were initially made in breast cancer but can be generalized to many other tumors, such as prostate, cervix or lung cancers.
Overall, the team identified a new key regulator of cancer metastasis and a new therapeutic strategy to block the deadly spread of cancer.
This pubication has been co-authored by Drs. Alain Chariot (WELBIO – ULiège) and Pierre Close (WELBIO – ULiège).
Reference : Jeschke et al (2021) Nat Cancer 2 : 611-628 doi : 10.1038/s43018-021-00223-7
Source : Press Release ULB