Download Gene Section PXN (paxillin) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Gene Section
Mini Review
PXN (paxillin)
Tiffany Pierson, Brendan C Stack Jr
Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, AR
72205, USA (TP, BCJrS)
Published in Atlas Database: August 2011
Online updated version : http://AtlasGeneticsOncology.org/Genes/PXNID41953ch12q24.html
DOI: 10.4267/2042/46936
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
Protein
Other names: FLJ16691
HGNC (Hugo): PXN
Location: 12q24.23
Local order: Information about the local order of PXN
can be found at ensembl.org.
Description
DNA/RNA
4 isoforms have been identified by alternative splicing.
The 1st isoform is the normal variant and is comprised
of 591 AA and weighs 68 kDa. The amino terminus
region contains 5 LD-motifs, while the carboxy
terminus contains 4 LIM-zinc binding domains. The
protein also contains a proline rich region and several
potential phosphorylation sites.
Description
Expression
The PXN gene is 55.314 kb and consists of 12 exons.
This gene is a member of the Human CCDS set:
CCDS44996, CCDS44997, CCDS44998.
Epithelium.
Transcription
Found in the cytoplasm closely apposed to the plasma
membrane at sites of focal adhesion to the extracellular
matrix.
The transcript is 3788 base pairs long. 4 isoforms have
been identified.
Pseudogene
Not known.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
100
Localisation
PXN (paxillin)
Pierson T, Stack BCJr
Function
presence of the A127T mutation between the LD1 and
LD2 regions of PXN with non small cell lung cancer
(Jagadeeswaran et al., 2008). A possible mechanism is
that mutations between the LD1 and 2 regions confer
resistance to calpain mediated proteolysis of PXN
(Cortesio et al., 2011). However, two later studies did
not find this mutation to exist in lung cancer or any
other solid tumor (Pallier et al., 2009; Kim et al., 2011).
Overexpression of PXN in non small cell lung cancer
has been reported with less controversy (Jagadeeswaran
et al., 2008; Zhao et al., 2010; Mackinnon et al., 2011).
The overexpression could possibly be due to
rearrangements on chromosome 12 (Wu et al., 2010).
Focal adhesion protein: This protein is a cytoskeletal
component involved in focal actin-membrane
attachments to the extracellular matrix. PXN can
interact with multiple structural molecules and
regulatory proteins to modulate adhesion, motility and
survival of the cell by changing actin dynamics. Some
PXN binding proteins have oncogenic equivalents,
allowing cells to bypass normal adhesion and GF
signaling cascades.
Regulation: PXN activity is regulated by various
kinases. Adhesion and GF's stimulate these kinases to
phosphorylate LD motifs or LIM domains. Molecules
such as Vinculin, FAK and SRC phosphorylate tyrosine
residues of the N-terminal LD motifs. This results in
recruitment of downstream effectors (like CRK) to
mediate changes in cell motility or in modulation of
gene expression via MAPK pathways. N-terminal
serine phosphorylation has also been identified.
Phosphorylation of serine and threonine residues of Cterminal LIM domains results in recruitment to focal
adhesions. Identification of the C-terminal kinases is
currently under investigation.
Abbreviations: CRK (CT10 sarcoma oncogene
cellular homolog ); FAK (focal adhesion kinase); GF
(growth factor); MAPK (mitogen activated protein
kinase); SRC (Rous sarcoma oncogene cellular
homolog).
Homology
Member of the paxillin family, containing the 4 LIMzinc binding domains.
Mutations
Germinal
Note
Metastatic potential was found to be directly related to
PXN levels (Cai et al., 2010). The relationship between
PXN and Her-2 expression is controversial. A study in
2007 found a direct relationship between the 2 markers
(Short et al., 2007) while a 2011 study found no such
link (Panousis et al., 2011).
Prostate cancer
Note
PXN up regulation was found to promote adhesion and
motility of prostate cancer cells (Bokobza et al., 2010).
To be noted
Note
The link between PXN mutations and increased growth
rate and invasion of cancer cells is controversial. On
the contrary, amplification and/or overexpression of
PXN has been consistently reported in the literature.
References
Not known.
Somatic
Several single nucleotide polymorphisms have been
identified. Point mutations between the LD1 and LD2
motifs have been associated with lung cancer, the
A127T mutation being the most frequent mutation
(Jagadeeswaran, et al., 2008).
Implicated in
Head and neck cancers
Note
PXN overexpression has been reported in various head
and neck cancers (Li et al., 2008; Dai et al., 2010; Shi
et al., 2010). Metallopanstimulin-1 expression has been
associated with reduced PXN levels and tumor growth
rate (Dai et al., 2010).
Lung cancer
Sattler M, Pisick E, Morrison PT, Salgia R. Role of the
cytoskeletal protein paxillin in oncogenesis. Crit Rev Oncog.
2000;11(1):63-76
Brown MC, Turner CE. Paxillin: adapting to change. Physiol
Rev. 2004 Oct;84(4):1315-39
Conway WC, Van der Voort van Zyp J, Thamilselvan V, Walsh
MF, Crowe DL, Basson MD. Paxillin modulates squamous
cancer cell adhesion and is important in pressure-augmented
adhesion. J Cell Biochem. 2006 Aug 15;98(6):1507-16
Short SM, Yoder BJ, Tarr SM, Prescott NL, Laniauskas S,
Coleman KA, Downs-Kelly E, Pettay JD, Choueiri TK, Crowe
JP, Tubbs RR, Budd TG, Hicks DG. The expression of the
cytoskeletal focal adhesion protein paxillin in breast cancer
correlates with HER2 overexpression and may help predict
response
to
chemotherapy:
a
retrospective
immunohistochemical
study.
Breast
J.
2007
MarApr;13(2):130-9
Deakin NO, Turner CE. Paxillin comes of age. J Cell Sci. 2008
Aug 1;121(Pt 15):2435-44
Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi
V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R,
Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC,
Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L,
Note
A significant correlation was found between the
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
Breast cancer
101
PXN (paxillin)
Pierson T, Stack BCJr
Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D,
Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V,
Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia R.
Paxillin is a target for somatic mutations in lung cancer:
implications for cell growth and invasion. Cancer Res. 2008
Jan 1;68(1):132-42
Li BZ, Lei W, Zhang CY, Zhou F, Li N, Shi SS, Feng XL, Chen
ZL, Hang J, Qiu B, Wan JT, Shao K, Xing XZ, Tan XG, Wang
Z, Xiong MH, He J. Increased expression of paxillin is found in
human oesophageal squamous cell carcinoma: a tissue
microarray study. J Int Med Res. 2008 Mar-Apr;36(2):273-8
Sheibani N, Tang Y, Sorenson CM. Paxillin's LD4 motif
interacts with bcl-2. J Cell Physiol. 2008 Mar;214(3):655-61
Pallier K, Houllier AM, Le Corre D, Cazes A, Laurent-Puig P,
Blons H. No somatic genetic change in the paxillin gene in
nonsmall-cell lung cancer. Mol Carcinog. 2009 Jul;48(7):581-5
Bokobza SM, Ye L, Kynaston HG, Jiang WG. Growth and
differentiation factor-9 promotes adhesive and motile capacity
of prostate cancer cells by up-regulating FAK and Paxillin via
Smad dependent pathway. Oncol Rep. 2010 Dec;24(6):1653-9
Dai Y, Pierson SE, Dudney WC, Stack BC Jr. Extraribosomal
function of metallopanstimulin-1: reducing paxillin in head and
neck squamous cell carcinoma and inhibiting tumor growth. Int
J Cancer. 2010 Feb 1;126(3):611-9
Cai H, Zhang T, Tang WX, Li SL. [Expression of paxillin in
breast cancer cell with high and low metastatic potentiality].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Jan;41(1):91-4
Shi J, Wang S, Zhao E, Shi L, Xu X, Fang M. Paxillin
expression levels are correlated with clinical stage and
metastasis in salivary adenoid cystic carcinoma. J Oral Pathol
Med. 2010 Aug 1;39(7):548-51
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2)
102
Wu DW, Cheng YW, Wang J, Chen CY, Lee H. Paxillin
predicts survival and relapse in non-small cell lung cancer by
microRNA-218
targeting.
Cancer
Res.
2010
Dec
15;70(24):10392-401
Zhao Y, Zhang X, Guda K, Lawrence E, Sun Q, Watanabe T,
Iwakura Y, Asano M, Wei L, Yang Z, Zheng W, Dawson D,
Willis J, Markowitz SD, Satake M, Wang Z. Identification and
functional characterization of paxillin as a target of protein
tyrosine phosphatase receptor T. Proc Natl Acad Sci U S A.
2010 Feb 9;107(6):2592-7
Cortesio CL, Boateng LR, Piazza TM, Bennin DA, Huttenlocher
A. Calpain-mediated proteolysis of paxillin negatively regulates
focal adhesion dynamics and cell migration. J Biol Chem. 2011
Mar 25;286(12):9998-10006
Kim MS, Yoo NJ, Lee SH. Absence of paxillin gene mutation in
lung cancer and other common solid cancers. Tumori. 2011
Mar-Apr;97(2):211-3
Mackinnon AC, Tretiakova M, Henderson L, Mehta RG, Yan
BC, Joseph L, Krausz T, Husain AN, Reid ME, Salgia R.
Paxillin expression and amplification in early lung lesions of
high-risk patients, lung adenocarcinoma and metastatic
disease. J Clin Pathol. 2011 Jan;64(1):16-24
Panousis D, Patsouris E, Lagoudianakis E, Pappas A,
Kyriakidou V, Voulgaris Z, Xepapadakis G, Manouras A,
Athanassiadou AM, Athanassiadou P. The value of TOP2A,
EZH2 and paxillin expression as markers of aggressive breast
cancer: relationship with other prognostic factors. Eur J
Gynaecol Oncol. 2011;32(2):156-9
This article should be referenced as such:
Pierson T, Stack BCJr. PXN (paxillin). Atlas Genet Cytogenet
Oncol Haematol. 2012; 16(2):100-102.