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A critical role of AMPK, and Akt, mTOR and Wnt survival signals for the growth control of colon and liver cancer cells with selenium
Author(s) -
YunKyoung Lee,
Park Song Yi,
Lee Won Sup,
Surh YoungJoon,
Kim YoungMin,
Park Ock Jin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb450
Subject(s) - ampk , pi3k/akt/mtor pathway , protein kinase b , wnt signaling pathway , cancer research , mtorc2 , rptor , chemistry , cell growth , amp activated protein kinase , microbiology and biotechnology , signal transduction , mtorc1 , biology , protein kinase a , kinase , biochemistry
Cancer cells generally exhibit the increased ability to survive, while the susceptibility to undergo apoptosis is strikingly depressed. Survival signals such as Akt, mTOR and Wnt/GSK3β are known to play an important role of cell's sensitivity to death. Recent studies suggest that AMPK acts as a major controller of cancer cell proliferation integrating growth factor signaling with cellular metabolism. The important ability of AMPK to inhibit mTOR or Akt suggests that there exists an intricate network involving AMPK, Akt and mTOR to control cancer growth. We used selenium to activate AMPK to determine whether AMPK activation can inhibit cancer cell growth through suppressing Akt, mTOR or Wnt/β‐catenin. We have found that selenium lost its ability of inhibiting mTOR of HT‐29 cells and Wnt components of Hep3B cells in the absence of AMPK. However, selenium could inhibit Akt regardless of AMPK. The activation of AMPK and deactivation of mTOR or Akt were observed in selenium‐treated xenograft models. These results suggest that there exists a complex interaction between AMPK and mTOR or Akt, Wnt components and the thorough mechanistic understanding of AMPK and survival signals can point an effective strategy for cancer prevention with dietary origin components. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (NO. R01‐2008‐000‐20131‐0)]