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KRAS activates JOSD2. 3 / 3
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"The pro-tumor effects are further reinforced by the reciprocal JOSD2 upregulation by activated KRAS, therefore forming a “JOSD2/KRAS positive feedback circuit” in CRC tumors."
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"As shown in Fig. 6e, f and Supplementary Fig. 9a, b, HY041004 remarkably suppressed the cell proliferation and colony formation of HT-29-KRAS in vitro, and the effect of HY041004 on HT-29-KRAS is significantly stronger than that on HT-29-KRAS , whereas KRAS covalent inhibitors MRTX-849 only selectively inhibited KRAS CRC cells (Supplementary Fig. 9b), suggesting the potential of JOSD2 inhibition as the promising pan-KRAS-mutation-targeting strategy."
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"Moreover, we verified that KRAS mutants, not wild-type KRAS, reciprocally upregulated JOSD2, thus forming a JOSD2/KRAS positive feedback circuit that significantly accelerated cell proliferation."
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