Novel KRAS•GTP-RanGAP1 Axis Drives Nuclear Export in Cancer
| Type | research |
|---|---|
| Area | Pancreas |
| Published(YearMonth) | 2412 |
| Source | https://pubmed.ncbi.nlm.nih.gov/39528835/#:~:text=.%202024%20Dec%3B5%2812%29%3A1902) |
| Tag | newsletter |
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| Date(of entry) |
A study in Nature Cancer uncovered a previously unknown oncogenic role of KRAS, distinct from its traditional signaling pathways. Researchers identified a complex between activated KRAS (KRAS•GTP) and RanGAP1 that promotes nuclear export of proteins via the XPO1 pathway, independently of canonical PI3K/AKT or RAF/MEK signaling. This novel interaction facilitates the cytoplasmic translocation of key proteins such as EZH2, which subsequently degrade tumor suppressors like DLC1, driving cancer progression. Blocking this nuclear export pathway enhanced the effectiveness of KRAS-targeted therapies and tumor suppressor restoration. These findings offer promising opportunities for developing new therapeutic combinations in KRAS-driven cancers.