Download Gene Section S100P (S100 calcium binding protein P) in Oncology and Haematology

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Gene Section
Review
S100P (S100 calcium binding protein P)
Sayka Barry, Tatjana Crnogorac-Jurcevic
Institute of Cancer, Barts and The London, Queen Mary's School of Medicine and Dentistry, Queen Mary,
University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom (SB, TCJ)
Published in Atlas Database: July 2008
Online updated version : http://AtlasGeneticsOncology.org/Genes/S100PID42196ch4p16.html
DOI: 10.4267/2042/44493
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
terminal half of the protein contains an unconventional
EF hand that binds calcium with lower affinity, while
the C-terminal is canonical and binds calcium with high
affinity. The connecting hinge region and the Cterminal extension are the most variable regions and
thus determine the functional specificity of S100 family
members, including S100P. In addition to Ca2+, S100P
also binds Zn2+ and Mg2+ and can form homo- and
heterodimers.
Identity
Other names: MIG9; S100E
HGNC (Hugo): S100P
Location: 4p16.1
DNA/RNA
Description
Expression
S100P gene contains two exons and one intron.
Genomic size of 3,332 bases.
S100P is expressed in various normal tissues including
placenta, lung, heart, kidney, bladder, skeletal muscle,
bone marrow, spleen, mammary epithelium, epidermis,
prostate gland, gastric and intestinal mucosa, and
malignant tissues such as pancreatic ductal
adenocarcinoma, pancreatic intraductal papillary
mucinous neoplasm, non-small-cell lung cancer,
melanoma, gastric adenocarcinoma, ovarian, breast,
colon and prostate carcinoma as well as in the body
fluids such as tear, pancreatic juice, blood and urine.
Transcription
1279 bases mRNA; 288 bases coding sequences. The
transcript is on Chromosome 4 at location 6,745,6976,749,797.
Pseudogene
None identified.
Protein
Localisation
Description
Cytoplasm, nucleus, also secreted in the culture media.
S100P protein consists of 95 amino acids with a
molecular weight of 10.4 kDa.
S100P is a Ca2+ binding protein that belongs to S100
family ("Soluble in 100% saturated solution with
ammonium sulfate") which was first isolated from
human placenta and is therefore designated as "P".
S100 family includes at least 26 members, which are
thought to be expressed only in vertebrates and are
present in a tissue and cell-specific manner. S100
proteins are characterized by common structural motifs
including 2 EF-hands (helix-loop-helix calcium binding
domains) with different affinities for calcium ions, a
central hinge region and the C-terminal extension. The
N-
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
Function
S100P is involved in diverse biological functions but
the exact role or mechanism of its action is still largely
unknown. Upon binding of calcium ions S100P
undergoes a conformational change that results in an
exposure of a hydrophobic surface which allows the
interaction with specific target proteins. To date,
several S100P interacting partners have been identified
including S100P binding protein S100PBP, EZR,
S100A1, ECD, CacyBP, RAGE, S100Z and S100A6,
but the consequences of their interactions are not fully
understood.
429
S100P (S100 calcium binding protein P)
Barry S, Crnogorac-Jurcevic T
Homology
Colorectal cancer
S100P shares 50% sequence identity with human
S100A1 and 44% identity with S100B.
Oncogenesis
In colon cancer, expression of S100P correlates with
resistance to chemotherapy and has also been
associated with doxorubicin resistance in colon cancer
cell lines.
Mutations
Note
Mutations have not been reported.
Breast cancer
Oncogenesis
S100P has been associated with immortalization of
breast cancer cells in vitro and tumour progression in
vivo. Higher level of S100P expression has also been
correlated with decreased survival in patients with
breast cancer.
Implicated in
Cancers
Disease
S100P has been associated with the progression of
several types of cancer including pancreatic, prostate,
non-small cell lung, breast, and colorectal cancer.
Oncogenesis
S100P has been implicated in migration, invasion,
proliferation and survival of cancer cells in vitro and
increased tumour growth in vivo. In fibroblasts, S100P
has been shown to function as an autocrine growth and
survival factor that enhanced cell proliferation and
survival by activating RAGE receptor through MAPK
and NF-kB signaling.
Other cancer types
Note
S100P is also expressed at higher levels in gastric,
ovarian and cervical carcinomas.
References
Becker T, Gerke V, Kube E, Weber K. S100P, a novel Ca(2+)binding protein from human placenta. cDNA cloning,
recombinant protein expression and Ca2+ binding properties.
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Pancreatic cancer
Bertram J, Palfner K, Hiddemann W, Kneba M. Elevated
expression of S100P, CAPL and MAGE 3 in doxorubicinresistant cell lines: comparison of mRNA differential display
reverse
transcription-polymerase
chain
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and
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Oncogenesis
The up-regulation of S100P is an early event in the
development of pancreatic cancer and its expression
increases throughout the progression of pancreatic
intraepithelial neoplasia (PanINs) to invasive
pancreatic ductal adenocarcinoma. S100P plays a
critical role in the maintenance of the structural
organization of intermediate filaments (cytokeratins 8,
18 and 19) and actin cytoskeleton, and its overexpression changes the phosphorylation status of the
actin regulatory protein cofilin. Over-expression of
S100P also increases the expression of S100A6 and
cathepsin D, both of which are involved in cellular
invasion. As S100P is expressed early in pancreatic
ductal adenocarcinoma and is secreted into body fluids,
it can serve as an useful diagnostic marker.
Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM,
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Prostate cancer
Oncogenesis
In prostate cancer over-expression of S100P increases
cell growth both in vitro and in vivo. S100P overexpression also up-regulates androgen receptor that
leads to prostate cancer progression. Its expression has
also been associated with poor clinical prognosis of
patients with this malignancy.
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Non-small-cell lung cancer
Oncogenesis
Higher levels of S100P have been correlated with
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patients with lung cancer. This may also serve as a
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Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
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S100P (S100 calcium binding protein P)
Barry S, Crnogorac-Jurcevic T
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This article should be referenced as such:
Identification of maspin and S100P as novel hypomethylation
targets in pancreatic cancer using global gene expression
profiling. Oncogene. 2004 Feb 26;23(8):1531-8
Barry S, Crnogorac-Jurcevic T. S100P (S100 calcium binding
protein P). Atlas Genet Cytogenet Oncol Haematol. 2009;
13(6):429-431.
Arumugam T, Simeone DM, Van Golen K, Logsdon CD.
S100P promotes pancreatic cancer growth, survival, and
invasion. Clin Cancer Res. 2005 Aug 1;11(15):5356-64
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(6)
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