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• W2303849675 abstract "The Na + /H + exchanger regulatory factor (NHERF) family of proteins is scaffolds that orchestrate interaction of receptors and cellular proteins. Previous studies have shown that NHERF1 functions as a tumor suppressor. The goal of this study is to determine whether the loss of NHERF2 alters colorectal cancer (CRC) progress. We found that NHERF2 expression is elevated in advanced-stage CRC. Knockdown of NHERF2 decreased cancer cell proliferation in vitro and in a mouse xenograft tumor model. In addition, deletion of NHERF2 in Apc Min/+ mice resulted in decreased tumor growth in Apc Min/+ mice and increased lifespan. Blocking NHERF2 interaction with a small peptide designed to bind the second PDZ domain of NHERF2 attenuated cancer cell proliferation. Although NHERF2 is known to facilitate the effects of lysophosphatidic acid receptor 2 (LPA 2 ), transcriptome analysis of xenograft tumors revealed that NHERF2-dependent genes largely differ from LPA 2 -regulated genes. Activation of β-catenin and ERK1/2 was mitigated in Apc Min/+ ; Nherf2 − /− adenomas. Moreover, Stat3 phosphorylation and CD24 expression levels were suppressed in Apc Min/+ ; Nherf2 − /− adenomas. Consistently, NHERF2 knockdown attenuated Stat3 activation and CD24 expression in colon cancer cells. Interestingly, CD24 was important in the maintenance of Stat3 phosphorylation, whereas NHERF2-dependent increase in CD24 expression was blocked by inhibition of Stat3, suggesting that NHERF2 regulates Stat3 phosphorylation through a positive feedback mechanism between Stat3 and CD24. In summary, this study identifies NHERF2 as a novel oncogenic protein and a potential target for cancer treatment. NHERF2 potentiates the oncogenic effects in part by regulation of Stat3 and CD24." @default.
• W2303849675 created "2016-06-24" @default.
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• W2303849675 date "2016-04-15" @default.
• W2303849675 modified "2023-10-14" @default.
• W2303849675 title "Deletion of Na⁺/H⁺ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24" @default.
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• W2303849675 doi "https://doi.org/10.1152/ajpgi.00419.2015" @default.
• W2303849675 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4836134" @default.
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