S100A11, an dual mediator for growth regulation of human keratinocytes.
We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca(++) or transforming growth factor beta. Exposure to either agent resulted in transfer of S100A11 to nuclei, where it induced p21(WAF1). In contrast, S100A11 has been shown to be overexpressed in many human cancers. To address this apparent discrepancy, we analyzed possible new functions of S100A11, and we provide herein evidence that 1) S100A11 is actively secreted by NHK; 2) extracellular S100A11 acts on NHK to enhance the production of epidermal growth factor family proteins, resulting in growth stimulation; 3) receptor for advanced glycation end products, nuclear factor-kappaB, Akt, and cAMP response element-binding protein are involved in the S100A11-triggered signal transduction; and 4) production and secretion of S100A11 are markedly enhanced in human squamous cancer cells. These findings indicate that S100A11 plays a dual role in growth regulation of epithelial cells.
Sakaguchi
Masakiyo
M
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikatachou, Okayama 700-8558, Japan.
Sonegawa
Hiroyuki
H
Murata
Hitoshi
H
Kitazoe
Midori
M
Futami
Jun-ichiro
J
Kataoka
Ken
K
Yamada
Hidenori
H
Huh
Nam-ho
NH
D002294:Carcinoma, Squamous Cell / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; C072337:S100A11 protein, human; D004815:Epidermal Growth Factor; D051057:Proto-Oncogene Proteins c-akt