Cancer Stem Cell News
Cell Therapy News
Dermal Cell News
Endothelial Cell News
ESC & iPSC News
Extracellular Matrix News
Hematopoiesis News
Hepatic Cell News
Human Immunology News
Immune Regulation News
Intestinal Cell News
Mammary Cell News
Mesenchymal Cell News
Muscle Cell News
Neural Cell News
Organoid News
Pancreatic Cell News
Prostate Cell News
Pulmonary Cell NewsALKBH5 gain- or loss-of function could effectively reverse LKB1 regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells.
[Cell Death & Disease]
7753456 {7753456:5KGEGPH2} apa 50 1 162698 https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3A%22zotpress-b793487cbd843443167a6878988b6846%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%225KGEGPH2%22%2C%22library%22%3A%7B%22id%22%3A7753456%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zhang%20et%20al.%22%2C%22parsedDate%22%3A%222021-05-20%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EZhang%2C%20D.%2C%20Ning%2C%20J.%2C%20Okon%2C%20I.%2C%20Zheng%2C%20X.%2C%20Satyanarayana%2C%20G.%2C%20Song%2C%20P.%2C%20Xu%2C%20S.%2C%20%26amp%3B%20Zou%2C%20M.-H.%20%282021%29.%20Suppression%20of%20m6A%20mRNA%20modification%20by%20DNA%20hypermethylated%20ALKBH5%20aggravates%20the%20oncological%20behavior%20of%20KRAS%20mutation%5C%2FLKB1%20loss%20lung%20cancer.%20%3Ci%3ECell%20Death%20%26amp%3B%20Disease%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%286%29%2C%201%26%23x2013%3B14.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41419-021-03793-7%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41419-021-03793-7%3C%5C%2Fa%3E%20%3Ca%20title%3D%27Cite%20in%20RIS%20Format%27%20class%3D%27zp-CiteRIS%27%20href%3D%27https%3A%5C%2F%5C%2Fwww.stemcellsciencenews.com%5C%2Fwp-content%5C%2Fplugins%5C%2Fzotpress%5C%2Flib%5C%2Frequest%5C%2Frequest.cite.php%3Fapi_user_id%3D7753456%26amp%3Bitem_key%3D5KGEGPH2%27%3ECite%3C%5C%2Fa%3E%20%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Suppression%20of%20m6A%20mRNA%20modification%20by%20DNA%20hypermethylated%20ALKBH5%20aggravates%20the%20oncological%20behavior%20of%20KRAS%20mutation%5C%2FLKB1%20loss%20lung%20cancer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Donghong%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jinfeng%22%2C%22lastName%22%3A%22Ning%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Imoh%22%2C%22lastName%22%3A%22Okon%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaoxu%22%2C%22lastName%22%3A%22Zheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ganesh%22%2C%22lastName%22%3A%22Satyanarayana%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ping%22%2C%22lastName%22%3A%22Song%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shidong%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ming-Hui%22%2C%22lastName%22%3A%22Zou%22%7D%5D%2C%22abstractNote%22%3A%22Oncogenic%20KRAS%20mutations%20combined%20with%20the%20loss%20of%20the%20LKB1%20tumor-suppressor%20gene%20%28KL%29%20are%20strongly%20associated%20with%20aggressive%20forms%20of%20lung%20cancer.%20N6-methyladenosine%20%28m6A%29%20in%20mRNA%20is%20a%20crucial%20epigenetic%20modification%20that%20controls%20cancer%20self-renewal%20and%20progression.%20However%2C%20the%20regulation%20and%20role%20of%20m6A%20modification%20in%20this%20cancer%20are%20unclear.%20We%20found%20that%20decreased%20m6A%20levels%20correlated%20with%20the%20disease%20progression%20and%20poor%20survival%20for%20KL%20patients.%20The%20correlation%20was%20mediated%20by%20a%20special%20increase%20in%20ALKBH5%20%28AlkB%20family%20member%205%29%20levels%2C%20an%20m6A%20demethylase.%20ALKBH5%20gain-%20or%20loss-of%20function%20could%20effectively%20reverse%20LKB1%20regulated%20cell%20proliferation%2C%20colony%20formation%2C%20and%20migration%20of%20KRAS-mutated%20lung%20cancer%20cells.%20Mechanistically%2C%20LKB1%20loss%20upregulated%20ALKBH5%20expression%20by%20DNA%20hypermethylation%20of%20the%20CTCF-binding%20motif%20on%20the%20ALKBH5%20promoter%2C%20which%20inhibited%20CTCF%20binding%20but%20enhanced%20histone%20modifications%2C%20including%20H3K4me3%2C%20H3K9ac%2C%20and%20H3K27ac.%20This%20effect%20could%20successfully%20be%20rescued%20by%20LKB1%20expression.%20ALKBH5%20demethylation%20of%20m6A%20stabilized%20oncogenic%20drivers%2C%20such%20as%20SOX2%2C%20SMAD7%2C%20and%20MYC%2C%20through%20a%20pathway%20dependent%20on%20YTHDF2%2C%20an%20m6A%20reader%20protein.%20The%20above%20findings%20were%20confirmed%20in%20clinical%20KRAS-mutated%20lung%20cancer%20patients.%20We%20conclude%20that%20loss%20of%20LKB1%20promotes%20ALKBH5%20transcription%20by%20a%20DNA%20methylation%20mechanism%2C%20reduces%20m6A%20modification%2C%20and%20increases%20the%20stability%20of%20m6A%20target%20oncogenes%2C%20thus%20contributing%20to%20aggressive%20phenotypes%20of%20KRAS-mutated%20lung%20cancer.%22%2C%22date%22%3A%222021-05-20%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41419-021-03793-7%22%2C%22ISSN%22%3A%222041-4889%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41419-021-03793-7%22%2C%22deleted%22%3A1%2C%22collections%22%3A%5B%2243ZBJFKZ%22%5D%2C%22dateModified%22%3A%222021-05-20T21%3A19%3A25Z%22%7D%7D%5D%7D
Zhang, D., Ning, J., Okon, I., Zheng, X., Satyanarayana, G., Song, P., Xu, S., & Zou, M.-H. (2021). Suppression of m6A mRNA modification by DNA hypermethylated ALKBH5 aggravates the oncological behavior of KRAS mutation/LKB1 loss lung cancer. Cell Death & Disease, 12(6), 1–14. https://doi.org/10.1038/s41419-021-03793-7 Cite
