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

Masakiyo Sakaguchi, Hitoshi Murata, Hiroyuki Sonegawa, Yoshihiko Sakaguchi, Junichiro Futami, Midori Kitazoe, Hidenori Yamada, Nam Ho Huh

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)35679-35686
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number49
DOIs
Publication statusPublished - Dec 7 2007

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Annexin A1
Cytosolic Phospholipases A2
Annexins
Epidermal Growth Factor
Epithelial Cells
Keratinocytes
Cell growth
Growth
Growth Disorders
Apoptosis
Squamous Cell Neoplasms
Neoplasms
Cathepsin D
Arachidonic Acid
Tumors
Signal Transduction
Cells
Enzymes

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 journalArticle

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