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Expression of the Wnt target gene phospholipase D1 (PLD1) is up-regulated in various carcinomas, including colorectal cancer (CRC). However, the mechanistic significance of its elevated expression in intestinal tumorigenesis remains unknown. In this study, we show that genetic and pharmacological targeting of PLD1 disrupts spontaneous and colitis-associated(More)
APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/β-catenin and Ras pathways could be an(More)
Estrogens are considered as a major risk factor of endometrial cancer. In this study, we identified a mechanism of tumorigenesis in which K-Ras protein is stabilized via estrogen signaling through the ER-α36 receptor. PKCδ was shown to stabilize K-Ras specifically via estrogen signaling. Estrogens stabilize K-Ras via inhibition of(More)
Mitochondrial respiration is required for hypoxia-inducible factor (HIF)-1α stabilization, which is important for tumor cell survival, proliferation, and angiogenesis. Herein, small molecules that inhibit HIF-1α protein stability by targeting mitochondrial energy production were screened using the Library of Pharmacologically Active Compounds and cell(More)
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