Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 37, Pages 32394-32403Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.207597
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Funding
- National Institutes of Health from the NHLBI [HL-36573]
- National Institutes of Health from the NIGMS [GM-78565]
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Cells contain a large pool of nonpumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of alpha 1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. A supplement of pNaKtide, a peptide derived from alpha 1 Na/K-ATPase, reduces the activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness of pNaKtide and suggest that the defect in Na/K-ATPase-mediated signal transduction may be targeted for developing new anticancer therapeutics.
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