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Gene Section
Review
SLIT2 (slit homolog 2 (Drosophila))
Kim Brussen
Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, Academic Medical Center,
University of Amsterdam, Amsterdam, The Netherlands (KB)
Published in Atlas Database: October 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/SLIT2ID42328ch4p15.html
DOI: 10.4267/2042/48865
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2013 Atlas of Genetics and Cytogenetics in Oncology and Haematology
exons, mostly encoding for one individual leucine rich
repeat.
This allows alternative splicing of the exons, without
altering the frame (Little et al., 2002). Three
alternatively spliced variants were identified after
screening of a human fetal brain cDNA library and
nucleotide database searching (Little et al., 2002).
These variants have been described by different groups
(Holmes et al., 1998; Itoh et al., 1998; Brose et al.,
1999).
The transcript described by Itoh et al. (1998) was
named SLIT2A, the transcript described by Holmes et
al. (1998) was named SLIT2B and the transcript
described by Brose et al. (1999) was named SLIT2C.
SLIT2B and SLIT2C lack exon 15. This exon encodes
for eight amino acids of unkown function (Holmes et
al., 1998; Brose et al., 1999; Little et al., 2002). In
addition, SLIT2C contains an additional exon. This
exon is located in an intron between exon 8 and 9 and
encodes for four amino acids (Little et al., 2002).
Between transcripts, differences can also be found in
the length of the 5'UTR and the 3'UTR. The relevance
of the differently spliced variants is unclear.
Identity
Other names: SLIL3, Slit-2
HGNC (Hugo): SLIT2
Location: 4p15.2
DNA/RNA
Note
SLIT2 is a member of the SLIT gene family. In
mammals, this family contains 3 genes named SLIT1,
SLIT2 and SLIT3.
Description
SLIT2A and SLIT2C have 37 coding exons, while
SLIT2B has 36 coding exons, spanning 365 kb of the
genome. All SLIT genes contain CpG islands in their
promoter regions and intron length and exon-intron
boundaries are highly similar (Little et al., 2002; Dallol
et al., 2005).
Transcription
The leucine rich repeat regions of the three human
SLIT genes contain a large number of very small
Genomic localization of SLIT2. The SLIT2 gene is shown in red, the surrounding genes in grey. The arrows indicate the direction of
transcription (NCBI, version 10 Jul 12).
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
245
SLIT2 (slit homolog 2 (Drosophila))
Brussen K
Map of the SLIT2 gene, direction from 5'UTR till 3'UTR. The direction of transcription is indicated by the arrow. Exons are depicted as
blue boxes. Within the first and the last exon, the 5'UTR and 3'UTR are depicted in yellow. There are three differently spliced variants of
SLIT2, named SLIT2A, SLIT2B and SLIT2C (Holmes et al., 1998; Itoh et al., 1998; Brose et al., 1999). Exons that are only present in one
of the transcripts are depicted in red (see below for further explanation). The length of the exons and introns is roughly indicated, but is
not up to scale. The size of the exons ranges from 12 base pairs up to 1790 base pairs, the size of the introns ranges from 110 base
pairs up to 198870 base pairs. For clarity, the exons are depicted larger than the introns. Below is indicated which protein domains are
encoded by particular exons. Based on ENSEMBL version 68 Juli 2012 transcripts ENST00000504154 (SLIT2A), ENST00000503823
(SLIT2B) and ENST00000503837 (SLIT2C). Information on protein domains encoded by particular exons was obtained from Little et al.,
2002.
Nguyen-Ba-Charvet and Chedotal, 2002). SLIT
proteins can be proteolytically cleaved within the EGFlike region, this has been shown to occur for SLIT2 and
for SLIT3 (Brose et al., 1999; Patel et al., 2001;
Condac et al., 2012). Differently spliced variants of the
SLIT2 protein exist, three of which were reported in
literature (Itoh et al., 1998; Holmes et al., 1998; Brose
et al., 1999). SLIT2A is 1529 amino acids long
(ENSEMBL protein ID ENSP00000422591), SLIT2B
is 1521 amino acids long (ENSEMBL protein ID
ENSP00000427548) and SLIT2C is 1525 amino acids
long (ENSEMBL protein ID ENSP00000422261).
Protein
Note
The extracellular matrix protein SLIT was first
identified in a genetic screen for mutations that affected
the dorsal-ventral patterning or the development of the
central nervous system in Drosophila (Anderson et al.,
1984; Seeger et al., 1993). SLIT homologues have
since been found in C. elegans and in vertebrates,
including mammals (Holmes et al., 1998; Itoh et al.,
1998; Brose et al., 1999; Holmes et al., 2001;
Vargesson et al., 2001; Gilthorpe et al., 2002). The
cognate receptor of the SLIT proteins is Roundabout or
ROBO (Kidd et al., 1998; Huminiecki et al., 2002).
Expression
In humans, SLIT2 is expressed both during embryonic
development and during adult life. It is expressed in the
fetal kidney and lung (Itoh et al., 1998) as well as in the
adult kidney (Wu et al., 2001), in the female
reproductive tract (endometrium, fallopian tube and
ovaries) (Dickinson et al., 2008; Duncan et al., 2010;
Dickinson et al;, 2011), the adrenal gland, the brain and
the spinal cord (Itoh et al., 1998) and in bone marrow
stromal and endothelial cells (Geutskens et al., 2012).
Description
In mammals there are three SLIT genes which encode
large ECM glycoproteins of about 200 kDa, comprising
a stretch of four leucine rich repeats (LRR) connected
by disulphide bonds, seven to nine epidermal growth
factor (EGF)-like domains, a domain named Agrin,
Laminin, Perlecan and SLIT (ALPS) or laminin G-like
module, and a C-terminal cystein knot (Rothberg and
Artavanis-Tsakonas, 1992; Hohenester et al., 1999;
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
246
SLIT2 (slit homolog 2 (Drosophila))
Brussen K
Domain organization of the SLIT protein from N-terminus to C-terminus. SS: N-terminal signal peptide; LRR: leucin-rich repeat;
EGF-like: epidermal growth factor-like domain; Lam-G like: Agrin, Laminin, Perlecan and SLIT (ALPS) or laminin G-like module; Cystein
knot: C-terminal cystein knot. The sciccors represent a proteolytic cleavage site. Adapted from a figure created by dr. S.B. Geutskens
(Leiden University Medical Center; Department of Immunohematology and Blood Transfusion and Einthoven laboratory for Experimental
Vascular Medicine; Leiden; The Netherlands).
For two of the differently spliced variants of SLIT2, the
expression pattern was examined in several fetal and
adult tissues. SLIT2A is expressed in the adult human
spinal cord and in low levels in the fetal lung and
kidney (Itoh et al., 1998), expression of SLIT2B can
also be detected outside the CNS in postnatal human
tissues (Holmes et al., 1998). SLIT2C is expressed in
the rat spinal cord during embryonic development
(Brose et al., 1999). The functional relevance of the
differently spliced variants is not clear.
repellent for ROBO-expressing axons (Brose et al.,
1999; Kidd et al., 1999; Long et al., 2004). Outside the
CNS, SLIT plays an important role during embryonic
development and in human pathology.
Neuronal guidance: SLIT proteins function as
chemorepellents throughout the central nervous system
to restrict the positioning of axons to their proper sites.
Deletion of SLIT2 resulted in defects in cortical
inhibitory neurons, commisural neurons and sensory
neurons (Nguyen-Ba-Charvet et al., 1999; Bagri et al.,
2002; Nguyen-Ba-Charvet et al., 2002; Plump et al.,
2002; Long et al., 2004; Unni et al., 2012). Cortical
inhibitory neurons (interneurons) modulate the
response of pyramidal cells to incoming signals,
thereby preventing overexcitation and maintaining the
balance between different signals. In rodents, they are
generated in the ventral telencephalon whereafter they
migrate into the cortex (reviewed by Rossignol, 2011).
Slit1/2 double knockout mice display an increased
interneuron proliferation and an increase in neuronal
process length and branching (Andrews et al., 2008).
Vertebrate commissural neurons first arise in the dorsal
spinal cord. Their axons are directed to the midline/
floorplate by the chemoattractants netrin and sonic
hedgehog. When these axons have reached the midline,
they cross it and turn longitudinally on the opposite
side, growing right alongside the midline/ floor plate
(reviewed by Dickson and Gilestro, 2006). Bagri et al.
(2002) reported a broad spectrum of neuronal defects in
Slit2 knockout or Slit1/Slit2 double knockout mice.
Without SLIT2, axons project erronuously in ventral
and medial directions. Without SLIT1 and SLIT2,
axons also travel to and cross the midline. These
defects occured in corticofugal, thalamocortical, and
callosal tracts (Bagri et al., 2002). The corpus callosum
defects were further investigated by Unni et al. (2012).
In Slit2 knockout mice, defects in corpus callosum
formation occurred. Axons stalled at the midline or
projected aberrantly. There was no phenotype in Slit1
knockout mice and only a mild phenotype in Slit3
knockout mice, but in Slit1/Slit2 double knockout mice
Localisation
SLIT is a secreted extracellular matrix protein that is
bound to the surface of the cell by the extracellular
matrix, mainly by heparan sulfates (Liang et al., 1999;
Ronca et al., 2001). It has been reported that both the
N-terminal part of SLIT2 (Hussain et al., 2006) and the
C-terminal part of SLIT2 and SLIT3 bind to heparin
and heparan sulfates (Ronca et al., 2001; Condac et al.,
2012). The interaction between SLIT proteins and
heparan-sulfates is not only important for the binding
of SLIT proteins to the extracellular matrix, but can
also increase the affinity of SLIT for ROBO (Hu et al.,
2001). Removal of heparan sulfates from the cell
surface abolishes the response to SLIT2 (Hu et al.,
2001; Hussain et al., 2006). Therefore, heparan-sulfates
are considered as important co-receptors in SLITROBO signalling (Inatani et al., 2003; Steigemann et
al., 2004; Hussain et al., 2006). The SLIT2 and the
SLIT3 protein can be proteolytically cleaved.
Following proteolytic cleavage of SLIT2, the 140kDa
N-terminal fragment remains tightly associated to the
cell surface, while the 50-60kDa C-terminal fragment is
more loosely attached and can also be detected in
conditioned medium (Brose et al., 1999; Wang et al.,
1999).
Function
The extracellular matrix protein SLIT binds to the
transmembrane receptor Roundabout or ROBO and has
a conserved role in axon guidance in the central
nervous system (CNS), where SLIT functions as a
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Brussen K
was expanded from the periphery to the interior of the
kidney. Consequently, the mice did not survive after
birth (Grieshammer et al., 2004).
Migration: SLITs not only regulate migration and
differentiation during embryogenesis, but also during
adult life. SLIT2 has been shown to inhibit the
chemotaxis of peripheral blood mononuclear cells,
leukocytes, neutrophils, macrophages, lymphocytes and
dendritic cells both in vitro and in vivo (Wu et al.,
2001; Guan et al., 2003; Chen et al., 2004; Kanellis et
al., 2004; Prasad et al., 2007; Tole et al., 2009; Ye et
al., 2010), while it enhanced the chemotaxis of
eosinophils in vivo (Ye et al., 2010).
In some cell types, such as endothelial cells, the
response to SLIT2 is more variable (Wang et al., 2003;
Kaur et al., 2008). The differential response of cells to
SLIT2 may be explained in part by cell-specific
downstream signaling cues. Ye et al. have shown that
the level of the SLIT-ROBO GTPase activating protein
1 is lower in eosinophils than in neutrophils. As a
consequence, CDC42 and PI3K are activated in
eosinophils, resulting in enhanced chemotaxis, whereas
CDC42 is inactivated in neutrophils, leading to
inhibition of chemotaxis (Ye et al., 2010).
Osteoblast differentiation: SLIT2 has also been
implicated in the regulation of osteoblast
differentiation. Sun et al. (2009) reported that
osteogenic differentiation was inhibited by SLIT2 in
vitro (Sun et al., 2009).
the phenotype was more severe than in Slit2 knockout
mice. In addition, in both Slit2 knockout and Slit1/2
double knockout mice, there was a mispositioning of
glial cells (Unni et al., 2012). In Slit1/2/3 triple
knockout mice, 72% of commisural axons failed to
leave the midline and 20% recrossed the midline (Long
et al., 2004). Olfactory sensory neurons located in the
olfactory epithelium pick up different odors and
translate these odors into sensory information for the
brain. Axons from the sensory neurons project into the
olfactory bulb (OB) into separate units that are specific
for one odor, the glomeruli. Dendrites from mitral and
tufted cells transmit the information from the different
glomeruli to the olfactory cortex of the brain.
The olfactory system is organized into distinct regions.
Odorants activate a typical pattern of glomeruli in
different regions of the OB. The distinct patterning of
the OB and the type and place of the activated
glomeruli determine the behavior elicited by an odorant
(Reviewed by Mori and Sakano, 2011).
In the developing mouse and rat olfactory system, Slit2
is the first repellent expressed in the septum, Slit1
follows. From E14 to E18, both are expressed in the
midline of the telencephalon including the septum. At
this stage, Robo2 is expressed by tufted and mitral cells
in the OB. In vitro, SLIT1 and SLIT2 repelled OB
axons (Nguyen-Ba-Charvet et al., 1999; Nguyen-BaCharvet et al., 2002). Moreover, in Slit1 and Slit2
double KO mice, axons were not repelled by the
midline and the septum. Correspondingly, the lateral
olfactory tract (LOT) was increased in size.
No defects were found in Slit1 or Slit2 single KO mice
(Nguyen-Ba-Charvet et al., 2002). Sensory neurons in
the visual pathway were also affected by Slit factors. In
Slit1/Slit2 knockout mice a second optic chiasm was
formed with aberrantly projecting axons (Plump et al.,
2002).
Kidney development: Development of the kidney is
initiated by the Wolfferian duct, which forms the
ureteric bud. The ureteric bud branches and further
develops in the ureters and the kidney. An important
growth factor during bud development is the TGF-β
family member glial cell-line-derived neurotrophic
factor (GDNF), which signals through a receptor
kinase, RET and is restricted to the site of ureteric bud
development.
Defects in ureteric bud development can result in
malformation of the kidney or ureters, renal agenesis or
a reduced number of nephrons (Costantini and Shakya,
2006).
In Slit2 mutant embryos, GDNF expression was not
restricted to the site of bud development and an
additional ureteric bud developed.
This resulted in the development of two or more ureters
or kidneys at the same site. The ureters failed to
connect to the bladder and the collecting ducts and the
ureter were dilated. Later during development, in some
of the embryos the kidneys fused. Nephron formation
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
Homology
A single slit gene was isolated in invertebrates, whereas
there are three SLIT genes in mammals. The human
SLIT2 protein shows 44,3 sequence homology to
Drosophila Slit (Itoh et al., 1998; Brose et al., 1999),
65% homology to the human SLIT1 protein (NCBI
accession BAA35184.1, NCBI protein blast) and 67%
homology to the human SLIT3 protein (NCBI
accession AAQ89243.1, NCBI protein blast).
Implicated in
Medulloblastoma
Note
86% of medulloblastoma tumors express SLIT2, which
is not silenced by methylation of the CpG islands.
Interestingly, administration of recombinant SLIT2
protein to medulloblastoma spheroids could inhibit
tumor cell invasion without affecting cell direction or
proliferation. Treatment with SLIT2 conditioned media
resulted in reduced CDC42 activation and moderately
reduced Rac1 activation. There was no effect on RhoA
activity (Werbowetski-Ogilvie et al., 2006).
Glioma
Note
Dallol et al. (2003) detected methylation of the CpG
islands in the SLIT2 promoter in 59% of gliomas and in
248
SLIT2 (slit homolog 2 (Drosophila))
Brussen K
attributed to deregulation of β-catenin and E-cadherin/
SNAI1 (Tseng et al., 2010).
71% of the tested glioma cell lines. 66,7% of the
gliomas were classified as glioblastoma multiforme, the
most malignant stage, the rest was randomly collected.
Promoter methylation correlated with reduced SLIT2
expression. Exogenous expression of SLIT2 in a
methylated glioma cell line suppressed tumor growth in
a colony formation assay (Dallol et al., 2003).
In another study, administration of SLIT2 to glioma
spheroids of a non-methylated cell line did not affect
tumor invasion (Werbowetski-Ogilvie et al., 2006).
Breast cancer
Note
Methylation of the SLIT2 promoter was discovered in
43% of breast cancer primary tumors and in 59% of
breast cancer cell lines, which correlated with reduced
SLIT2 expression in these tumors. In breast tumor cell
lines, both overexpression of SLIT2 and treatment with
SLIT2 conditioned media suppressed tumor cell growth
in an in vitro colony assay (Dallol et al., 2002).
Overexpression of SLIT2 also reduced proliferation
and migration in vitro (Prasad et al., 2008). There was
no effect on breast cancer cell lines with a normal
expression level of SLIT2 (Dallol et al., 2002).
In mice injected with SLIT2 overexpressing MCF-7
breast cancer cells, tumor size was reduced (Prasad et
al., 2008). The tumor-suppressive effect of SLIT2 may
be mediated via 2 different mechanisms, namely
through the modulation of β-catenin signaling and
through the modulation of CXCL12/ CXCR4-signaling.
Overexpression of SLIT2 resulted in increased cell-cell
adhesion due to enhanced β-catenin-E-cadherin
association. This was combined with decreased
expression of β-catenin and target genes of β-catenin,
decreased nuclear translocation of β-catenin and
increased expression of E-cadherin (Prasad et al.,
2008).
Several studies found a correlation between CXCR4
and SLIT expression in breast cancer cells. Loss of
SLIT2 and SLIT3 expression correlated with the
upregulation of CXCR4 and resulted in hyperplastic
lesions and in desmoplastic stroma in mouse mammary
gland and in human MCF7 breast cancer cells.
Overexpression of SLIT2 or SLIT3 in human breast
carcinoma MDA-MB-231 cells resulted in a downregulation of CXCR4 expression, reduced colony
formation in vitro and in inhibition of tumor growth in
a xenograft model in vivo.
Furthermore, SLIT2 addition inhibited CXCL12/
CXCR4-induced breast cancer cell chemotaxis, chemoinvasion and adhesion.
Colorectal carcinoma
Note
In 72% of colorectal carcinomas, methylation of the
SLIT2 promoter was found, which correlated with
abolished expression of SLIT2. Exogenous expression
of SLIT2 in two methylated colorectal tumor cell lines
suppressed tumor growth in a colony formation assay.
In addition, administration of SLIT2 conditioned
medium suppressed tumor growth and induced
apoptosis in a methylated colorectal tumor cell line
(Dallol et al., 2003).
In contrast, Wang et al. (2003) reported that SLIT2
expression was not detected in normal and hyperplastic
colon tissues, was moderately detected in colon
adenomas (21,4%) and was upregulated in 64,6% of
colon carcinomas.
SLIT2 expression appeared to be enhanced in areas of
high tumor cell and vessel density. Blood vessel growth
and tumor volume increased in athymic nude mice
injected with melanoma cells that overexpress SLIT2,
but it was not investigated whether this occurs in colon
cancer cells (Wang et al., 2003).
Lung cancer
Note
Methylation of the SLIT2 promoter was found in 53%
of primary non-small cell lung cancer (NSCLC)
tumors, in 77% of NSCLC cell lines, in 36% of primary
small cell lung cancer (SCLC) tumors and in 55% of
SCLC cell lines (Dallol et al., 2002; Tseng et al., 2010),
which correlated with reduced SLIT2 expression
(Tseng et al., 2010). Furthermore, low SLIT2
expression correlated with a poor prognosis and lower
disease-free survival rates in NSCLC patients.
For patients with metastasis, the poor survival rate
correlated not only with low SLIT2 expression but also
with accumulation of β-catenin (Tseng et al., 2010).
When SLIT2 was re-expressed after treatment with
demethylating agents, the migration of lung cancer
cells decreased, while β-catenin-E-cadherin association
was enhanced.
Moreover, migration was also inhibited when the cells
were treated with SLIT2 conditioned media or after
exogenous expression of SLIT2 in the cells. Besides
reduced migration, these cells had increased E-cadherin
and decreased SNAI1 levels. On the contrary, after
knock down of SLIT2, migration was increased while
cell adhesion was reduced. Reduced cell adhesion was
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
SLIT2 affects CXCR4 signaling via the inhibition of
CXCL12-induced phosporylation of focal adhesion
components and the inhibition of PI3K, MAPK and
metallo-protease activity (Prasad et al., 2004, Marlow
et al., 2008).
Melanoma
Note
SLIT2 was expressed in 42,9% of melanomas, while
SLIT2 was not expressed in nearby normal tissue.
Blood vessel growth and tumor volume increased in
athymic nude mice injected with melanoma cells that
overexpress SLIT2, while both were decreased when
SLIT-ROBO signaling was inhibited by ectopic
expression of ROBON, an extracellular fragment which
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SLIT2 (slit homolog 2 (Drosophila))
Brussen K
Nguyen Ba-Charvet KT, Brose K, Marillat V, Kidd T, Goodman
CS, Tessier-Lavigne M, Sotelo C, Chédotal A. Slit2-Mediated
chemorepulsion and collapse of developing forebrain axons.
Neuron. 1999 Mar;22(3):463-73
contains the SLIT-binding domain of ROBO1 and
functions as scavenger for SLIT proteins, or the use of
R5, an antibody directed against the SLIT-binding
domain of ROBO1 (Wang et al., 2003).
Wang KH, Brose K, Arnott D, Kidd T, Goodman CS, Henzel W,
Tessier-Lavigne M. Biochemical purification of a mammalian
slit protein as a positive regulator of sensory axon elongation
and branching. Cell. 1999 Mar 19;96(6):771-84
Lymphatic metastasis of pancreatic islet
tumors
Note
Administration of SLIT2 to human lymphatic
endothelial cells (hLEC) resulted in enhanced tubular
formation and in increased migration, while there was
no effect on the proliferation of the cells.
Overexpression of Slit2 resulted in an increase of
lymphatic vessel length in the pancreas. When Slit2
transgenic mice were crossed with the non-metastatic
pancreatic islet tumor mouse line RIP1-Tag2, tumor
lymphangiogenesis was increased and metastases in the
regional mesentheric lymph nodes and in the intestines
were found. Although some metastases were found in
control mice, metastasis formation was higher in mice
that overexpress Slit2 and overall survival was
decreased (Yang et al., 2010).
Holmes G, Niswander L. Expression of slit-2 and slit-3 during
chick development. Dev Dyn. 2001 Oct;222(2):301-7
Hu H. Cell-surface heparan sulfate is involved in the repulsive
guidance activities of Slit2 protein. Nat Neurosci. 2001
Jul;4(7):695-701
Patel K, Nash JA, Itoh A, Liu Z, Sundaresan V, Pini A. Slit
proteins are not dominant chemorepellents for olfactory tract
and
spinal
motor
axons.
Development.
2001
Dec;128(24):5031-7
Ronca F, Andersen JS, Paech V, Margolis RU.
Characterization of Slit protein interactions with glypican-1. J
Biol Chem. 2001 Aug 3;276(31):29141-7
Vargesson N, Luria V, Messina I, Erskine L, Laufer E.
Expression patterns of Slit and Robo family members during
vertebrate limb development. Mech Dev. 2001 Aug;106(12):175-80
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Dickinson RE, Myers M, Duncan WC.. Novel regulated
expression of the SLIT/ROBO pathway in the ovary: possible
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Chen B, Blair DG, Plisov S, Vasiliev G, Perantoni AO, Chen Q,
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interact with Slits and act as negative regulators of monocyte
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Grieshammer U, Le Ma, Plump AS, Wang F, Tessier-Lavigne
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Conserved roles for Slit and Robo proteins in midline
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Tole S, Mukovozov IM, Huang YW, Magalhaes MA, Yan M,
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LA.. The axonal repellent, Slit2, inhibits directional migration of
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Heparan sulfate proteoglycan syndecan promotes axonal and
myotube guidance by slit/robo signaling. Curr Biol. 2004 Feb
3;14(3):225-30
Duncan WC, McDonald SE, Dickinson RE, Shaw JL, Lourenco
PC, Wheelhouse N, Lee KF, Critchley HO, Horne AW..
Expression of the repulsive SLIT/ROBO pathway in the human
endometrium and Fallopian tube. Mol Hum Reprod. 2010
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Wang YC.. SLIT2 attenuation during lung cancer progression
deregulates beta-catenin and E-cadherin and associates with
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Costantini F, Shakya R.. GDNF/Ret signaling and the
development of the kidney. Bioessays. 2006 Feb;28(2):117-27.
(REVIEW)
Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
251
SLIT2 (slit homolog 2 (Drosophila))
Brussen K
Yang XM, Han HX, Sui F, Dai YM, Chen M, Geng JG.. SlitRobo signaling mediates lymphangiogenesis and promotes
tumor lymphatic metastasis. Biochem Biophys Res Commun.
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Epub 2010 May 8.
Condac E, Strachan H, Gutierrez-Sanchez G, Brainard B,
Giese C, Heiss C, Johnson D, Azadi P, Bergmann C, Orlando
R, Esmon CT, Harenberg J, Moremen K, Wang L.. The Cterminal fragment of axon guidance molecule Slit3 binds
heparin and neutralizes heparin's anticoagulant activity.
Glycobiology.
2012
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Ye BQ, Geng ZH, Ma L, Geng JG.. Slit2 regulates attractive
eosinophil and repulsive neutrophil chemotaxis through
differential srGAP1 expression during lung inflammation. J
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2010
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Geutskens SB, Andrews WD, van Stalborch AM, Brussen K,
Holtrop-de Haan SE, Parnavelas JG, Hordijk PL, van Hennik
PB.. Control of human hematopoietic stem/progenitor cell
migration by the extracellular matrix protein Slit3. Lab Invest.
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2012 May 21.
Dickinson RE, Fegan KS, Ren X, Hillier SG, Duncan WC..
Glucocorticoid regulation of SLIT/ROBO tumour suppressor
genes in the ovarian surface epithelium and ovarian cancer
cells.
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Unni DK, Piper M, Moldrich RX, Gobius I, Liu S, Fothergill T,
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Slits regulate the development of midline glial populations and
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Atlas Genet Cytogenet Oncol Haematol. 2013; 17(4)
This article should be referenced as such:
Brussen K. SLIT2 (slit homolog 2 (Drosophila)). Atlas Genet
Cytogenet Oncol Haematol. 2013; 17(4):245-252.
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