Abstract
Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A2 (cPLA 2), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca 2+-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA2, resulting in inhibition of cPLA2 activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp12, and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 35679-35686 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 282 |
| Issue number | 49 |
| DOIs | |
| Publication status | Published - Dec 7 2007 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Truncation of annexin A1 is a regulatory lever for linking epidermal growth factor signaling with cytosolic phospholipase A2 in normal and malignant squamous epithelial cells. / Sakaguchi, Masakiyo; Murata, Hitoshi; Sonegawa, Hiroyuki; Sakaguchi, Yoshihiko; Futami, Junichiro; Kitazoe, Midori; Yamada, Hidenori; Huh, Nam Ho.
In: Journal of Biological Chemistry, Vol. 282, No. 49, 07.12.2007, p. 35679-35686.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Truncation of annexin A1 is a regulatory lever for linking epidermal growth factor signaling with cytosolic phospholipase A2 in normal and malignant squamous epithelial cells
AU - Sakaguchi, Masakiyo
AU - Murata, Hitoshi
AU - Sonegawa, Hiroyuki
AU - Sakaguchi, Yoshihiko
AU - Futami, Junichiro
AU - Kitazoe, Midori
AU - Yamada, Hidenori
AU - Huh, Nam Ho
PY - 2007/12/7
Y1 - 2007/12/7
N2 - Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A2 (cPLA 2), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca 2+-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA2, resulting in inhibition of cPLA2 activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp12, and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.
AB - Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A2 (cPLA 2), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca 2+-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA2, resulting in inhibition of cPLA2 activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp12, and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.
UR - http://www.scopus.com/inward/record.url?scp=37249087083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37249087083&partnerID=8YFLogxK
U2 - 10.1074/jbc.M707538200
DO - 10.1074/jbc.M707538200
M3 - Article
C2 - 17932043
AN - SCOPUS:37249087083
VL - 282
SP - 35679
EP - 35686
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 49
ER -