Abstract:
:Despite the progress made in targeted anticancer therapies in recent years, challenges remain. The identification of new potential targets will ensure that the arsenal of cancer therapies continues to expand. FAM83B was recently discovered in a forward genetic screen for novel oncogenes that drive human mammary epithelial cell (HMEC) transformation. We report here that elevated FAM83B expression increases Phospholipase D (PLD) activity, and that suppression of PLD1 activity prevents FAM83B-mediated transformation. The increased PLD activity is engaged by hyperactivation of epidermal growth factor receptor (EGFR), which is regulated by an interaction involving FAM83B and EGFR. Preventing the FAM83B/EGFR interaction by site-directed mutation of lysine 230 of FAM83B suppressed PLD activity and MAPK signaling. Furthermore, ablation of FAM83B expression from breast cancer cells inhibited EGFR phosphorylation and suppressed cell proliferation. We propose that understanding the mechanism of FAM83B-mediated transformation will provide a foundation for future therapies aimed at targeting its function as an intermediary in EGFR, MAPK and mTOR activation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Cipriano R,Bryson BL,Miskimen KL,Bartel CA,Hernandez-Sanchez W,Bruntz RC,Scott SA,Lindsley CW,Brown HA,Jackson MWdoi
10.1038/onc.2013.293subject
Has Abstractpub_date
2014-06-19 00:00:00pages
3298-306issue
25eissn
0950-9232issn
1476-5594pii
onc2013293journal_volume
33pub_type
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