The role of cadherin/catenin complex in malignant melanoma
In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadherins represent the most important superfamily of adhesion molecules with epithelial E-cadherin being the most studied. Its role in normal state as well as in cancer inv...
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irk-123456789-1379212018-06-18T03:04:52Z The role of cadherin/catenin complex in malignant melanoma Bonitsis, N. Batistatou, A. Karantima, S. Charalabopoulos, K. In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadherins represent the most important superfamily of adhesion molecules with epithelial E-cadherin being the most studied. Its role in normal state as well as in cancer invasion and metastasis and some other pathologies is crucial. E-cadherin expression is altered in malignant melanomas and its downregulation or absence is associated with melanoma invasion and metastasis potential. A shift from E-cadherin expression to neural N-cadherin expression in melanocytes is also detected in malignant melanomas formation. In addition, a discussion regarding the role of placental P-cadherin and vascular endothelial VE-cadherin as well as the recently identified molecule of dysadherin, is attempted in brief. В обзоре обсуждается роль кадгерин/катенинового комплекса при злокачественной меланоме. Кадгерины представляют собой суперсемейство адгезивных молекул, среди которых наиболее изучен эпителиальный кадгерин (E-кадгерин), выполняющий ключевую роль в норме и при инвазивном опухолевом росте и метастазировании. В ткани злокачественных меланом уровень экспрессии E-кадгерина изменен, его снижение или отсутствие связано с инвазивным ростом и метастазированием опухоли. При образовании злокачественных меланом в меланоцитах отмечают замену экспрессии E-кадерина на таковую неврального кадгерина (N-кадгерина). Кроме того, коротко обсуждается роль плацентарного кадгерина (P-кадгерина), эндотелиального кадгерина сосудов (VE-кадерина) и недавно идентифицированного дисадгерина. 2006 Article The role of cadherin/catenin complex in malignant melanoma / N. Bonitsis, A. Batistatou, S. Karantima, K. Charalabopoulos // Experimental Oncology. — 2006. — Т. 28, № 3. — С. 187-193. — Бібліогр.: 78 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137921 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadherins represent the most important superfamily of adhesion molecules with epithelial E-cadherin being the most studied. Its role in normal state as well as in cancer invasion and metastasis and some other pathologies is crucial. E-cadherin expression is altered in malignant melanomas and its downregulation or absence is associated with melanoma invasion and metastasis potential. A shift from E-cadherin expression to neural N-cadherin expression in melanocytes is also detected in malignant melanomas formation. In addition, a discussion regarding the role of placental P-cadherin and vascular endothelial VE-cadherin as well as the recently identified molecule of dysadherin, is attempted in brief. |
| format |
Article |
| author |
Bonitsis, N. Batistatou, A. Karantima, S. Charalabopoulos, K. |
| spellingShingle |
Bonitsis, N. Batistatou, A. Karantima, S. Charalabopoulos, K. The role of cadherin/catenin complex in malignant melanoma Experimental Oncology |
| author_facet |
Bonitsis, N. Batistatou, A. Karantima, S. Charalabopoulos, K. |
| author_sort |
Bonitsis, N. |
| title |
The role of cadherin/catenin complex in malignant melanoma |
| title_short |
The role of cadherin/catenin complex in malignant melanoma |
| title_full |
The role of cadherin/catenin complex in malignant melanoma |
| title_fullStr |
The role of cadherin/catenin complex in malignant melanoma |
| title_full_unstemmed |
The role of cadherin/catenin complex in malignant melanoma |
| title_sort |
role of cadherin/catenin complex in malignant melanoma |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2006 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/137921 |
| citation_txt |
The role of cadherin/catenin complex in malignant melanoma / N. Bonitsis, A. Batistatou,
S. Karantima, K. Charalabopoulos // Experimental Oncology. — 2006. — Т. 28, № 3. — С. 187-193. — Бібліогр.: 78 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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| first_indexed |
2025-07-10T02:41:20Z |
| last_indexed |
2025-07-10T02:41:20Z |
| _version_ |
1837226035357155328 |
| fulltext |
Experimental Oncology 28, 187–193, 2006 (September) 187
The role of cell adhesion mechanisms is of vital
significance in very important cell features. Basic
processes such as embryogenesis, tissue and organ
pattern formation and tissue architecture are some
of them. It is believed that changes in cell adhesion
molecules are implicated in the loss of control of cell
proliferation and neoplasia. The adhesion molecules
support and direct the exchange of information bet
ween two cells; they are not just molecular glue [1].
Deregulation and loss of control of cellcell interactions
is often associated with the establishment of new in
teractions and the metastasis process [2, 3]. Various
classes of cellcell adhesion molecules are expressed
in various human tissues and in the skin as well [4]. At
present, adhesion molecules embrace five categories:
cadherins, integrins, immunoglobulin gene superfami
ly members, selectins and CD44.
Cadherins constitute a large superfamily of adhe
sion molecules. They are transmembraneous gly
coproteins that connect one cell to another through
calcium iondependent binding [5, 6]. Cadherins are
important for the intercellular contacts in solid tissues.
They form the transembrane part of the adherent
junctions. Among them E (epithelial), N (neural),
P (placental) and VE (vascular endothelial) cadherins
are the better studied [7, 8]. These adhesive molecules
consist of five extracellular domains and a conserved
cytoplasmic region. Intracellularly, cadherins bind to a
catenin molecule providing a link to the cytoskeleton
[8]. Each member of the cadherins superfamily has a
specific binding site allowing binding between cadhe
rins of the same subtype in a homophilic fashion [9].
The complex molecular interactions allow cadherins
to take part in intercellular communication. They can
modulate in both normal and malignant tissues all
functions and differentiation processes. One of those
functions is the determination of the location of the
melanocytes in the skin. However, during migration
melanocyte precursors do not express E or Pcadhe
rin [8]. Inactivation of cadherins leads to disruption
of the cellcell adhesion. In contrast, inactivation of
other adhesion systems, apart from cadherins, has a
little effect on adhesion [10]. Except of the sensitivity
of cadherins to act in the absence of calcium ions,
cadherin function is also disrupted in carcinomas. In
particular, loss of Ecadherin expression in human
carcinoma cells is associated with invasiveness and
dedifferentiation of carcinoma cells [11].
Catenins, which are undercoated cytoplasmic
proteins, represent very important molecules strongly
associated with the expression and function of cadher
ins. Catenins (α, β and γ) are proteins with a specific
cytoplasmic domain crucial in cadherin function. They
link cadherins to the actin filaments network as well
as to other transmembrane and cytoplasmic proteins
[1]. The part of the cadherin which links to the actin
cytoskeleton is the cytoplasmic tail of the cadherin.
The three members (α, β, and γcatenin) compose
the catenin family, with αcatenin playing an important
role in adhesion [12]. Furthermore, the p120 molecule
is regarded to be a new catenin molecule similar to that
of γcatenin. It has been shown that the expression
of α and γcatenin is reduced or absent in melano
cytic nevi and melanomas [13]. Altered expression of
catenins is suggested to be associated with the de
velopment of the melanocytic lesions. Heterogenous
expression of catenins in the same lesion strongly
suggests that catenins may be involved in different
adhesion mechanisms. No correlation among the
various types of catenins was shown regarding their
expression pattern in the same study [13]. It must be
mentioned that γcatenin expression is commonly
reduced in melanomas, in contrast to βcatenin which
is overexpressed, suggesting a possible indirect role
THE ROLE OF CADHERIN/CATENIN COMPLEX IN MALIGNANT
MELANOMA
N. Bonitsis1, 2, A. Batistatou3, S. Karantima1, K. Charalabopoulos1, *
1Department of Physiology, Clinical Unit, Ioannina University Medical School, Ioannina, Greece
2Department of Dermatology, Ioannina University Medical School, Ioannina, Greece
3Department of Pathology, Ioannina University Medical School, Ioannina, Greece
In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadhe
rins represent the most important superfamily of adhesion molecules with epithelial Ecadherin being the most studied. Its role in
normal state as well as in cancer invasion and metastasis and some other pathologies is crucial. Ecadherin expression is altered
in malignant melanomas and its downregulation or absence is associated with melanoma invasion and metastasis potential. A shift
from Ecadherin expression to neural Ncadherin expression in melanocytes is also detected in malignant melanomas formation.
In addition, a discussion regarding the role of placental Pcadherin and vascular endothelial VEcadherin as well as the recently
identified molecule of dysadherin, is attempted in brief.
Key Words: adhesion molecules, cadherins, catenins, dysadherin, melanoma.
Received: August 2, 2006.
*Correspondence: Fax: 003 26510 97850
E-mail: kcharala@cc.uoi.gr
Abbreviations used: E-cadherin — epithelial cadherin;
N-cadherin – neural cadherin; P-cadherin – placental cadherin;
VE-cadherin — vascular endothelial cadherin.
Exp Oncol 2006
28, 3, 187–193
188 Experimental Oncology 28, 187–193, 2006 (September)
of βcatenin as an oncogene in melanoma cases
[13]. In the same study, βcatenin was found to be
expressed by all benign and malignant melanocytic
lesions [13]. Finally, loss of αcatenin expression was
directly associated with melanoma progression [13].
The most important changes in cadherin and catenin
expression were observed during the vertical growth
phase of melanomas. Loss of membranous Pcadhe
rin and βcatenin expression, minimal membranous
Ecadherin expression, as well as loss/minor de novo
membranous Ncadherin expression, represent al
terations commonly found in melanoma progression
processes. As a result of these changes mentioned just
above, cells lose their adhesive capacity and decline
their resistance to tumorigenetic process [14].
MELANOMA
One of the fastest rising malignancies in the last
years turns to be cutaneous melanoma [15]. Generally
melanoma begins with benign nevi and progresses to
radical and vertical growth [16, 17]. Between those
phases melanocytic nevus with lentiginous melano
cytic hyperplasia and aberrant differentiation and/or
melanocytic dysplasia may occur. Finally, metastases
may occur after the vertical phase growth [18]. This
propensity of melanoma to metastasise is the most
important characteristic that distinguishes it from other
types of cutaneous malignancies. The appearance of
melanoma may vary regardless the tumor site. Color
may also vary from gray or brown to black, red or even
dark blue [5, 19, 20].
Solid tumors are characterized by loss of cellular
and morphological features, uncontrolled proliferation,
invasiveness and colonization of cancer cells to distant
organs. It is believed that at least in part this is due to
changes taking place in the microenvironment of nor
mal cells and alterations in intercellular communication
between neoplastic and normal cells [21]. Melanocytes
are located in the basal layer of the epidermis and they
maintain during life a stableratio of 1:5 with basal ke
ratinocytes [22]. Melanocytes protect keratinocytes
through synthesis and donation of melanin after the
effect of ultraviolet light action [10]. In cases of nevis or
melanomas this balance is not kept and the transforma
tion disturbs the regulated induction of melanocyte divi
sion. In normal state, homeostasis, which determines if
a cell remains quiescent, proliferates, differentiates, or
undergoes apoptosis, should be maintained [23]. The
intercellular adhesion of melanocytes with keratino
cytes is achieved by adherent and regulatory junctions
via participation of Ecadherin molecules. Cadherins
without linkage to the actin cytoskeleton may undergo
weaker interactions. These cells are believed to be more
prone to cell migration [24].
In normal state, the established adhesion bet
ween melanocytes and keratinocytes controls the
melanocyte growth and the expression of cell surface
receptors. The contacts between keratinocytes and
melanocytes are established with the extension of
melanocytes’ dendrites that contribute to the estab
lishment of multiple contacts. When control process
is lost, then melanoma cells escape and melanoma
tumorigenesis is started. A shift in the expression of
Ecadherin, Pcadherin and desmoglein mainly to
Ncadherin is observed in melanoma cells. As a re
sult the anchorage to the basement membrane is lost
and homeostasis mechanisms are dysregulated. The
dysregulation of the balance of the epidermal melanin
units triggers a continuous proliferation of melanocytes
leading, finally, to melanoma development [25, 26]. It
has been shown that loss of regulatory dominance by
keratinocytes occurs in concert with downregulation of
Ecadherin expression in melanomas [27]. Functional
Ecadherin in melanoma cells is believed to lead to
cell adhesion to keratinocytes, protecting thus from
motility, proliferation and invasion [28]. Through the
complex process of metastasis, tumor cells undergo
drastic changes in cell shape and a reorganization of
the actin cytoskeleton is observed [29]. Cells separate
from the primary tumor mass and migrate through the
extracellular matrix, survive in the vascular system and
extravasate into foreign environments forming the me
tastases sites [30]. In contrast, normal melanocytes
appear heterotypic gap junctional intercellular com
munication with keratinocytes [31]. Loss of adhesion to
their original neighbors is one of the first steps, which
plays significant role in the invasion of melanoma into
adjacent tissues as well as in metastasis sites [10].
E-CADHERIN IN MELANOMAS
Ecadherin is a transmembrane glycoprotein locali
zed in the adherence junctions mediating celltocell
adhesion through calciumdependent homotypic
interactions [32]. Ecadherin is the most important
molecule in the interactions between melanocytes and
keratinocytes. Under normal conditions, Ecadherin
is expressed on the cell surface of keratinocytes and
melanocytes. If Ecadherin is not expressed, keratino
cytes cannot interact with the melanocytes, which now
are not regulated by the first [10]. Apart from the cell
tocell interactive role of Ecadherin, it is regarded that
it also suppresses epithelial tumor invasiveness and
metastasis [6, 33, 34]. Keratinocyte mediated control,
such as coordinated proliferation and downregulation
of metastasis, is restored by forced Ecadherin expres
sion in melanoma cells [35]. All epidermal layers in hu
man adult and infant skin, including skin appendages,
express on their cell surfaces Ecadherin [1]. Ecadhe
rin distribution on all of the plasma membranes of
keratinocytes was detected by ultrastructural studies
[36]. Ecadherin expression was absent on dermal sur
faces of basal cells [36]. However, dense deposits of
Ecadherin in the intercellular spaces of desmosomes
were observed [36]. Furthermore, it is revealed by
immunohistochemical studies that the normal human
epidermal melanocytes express E and Pcadherin in
contrast to melanoma cells [37]. This fact was proved
by the use of melanoma cell lines, which did not react
with antibodies against human E and Pcadherin [37].
When Ecadherin is not expressed, melanoma cells
Experimental Oncology 28, 187–193, 2006 (September) 189
escape from the control through keratinocytes. This
downregulation of Ecadherin is associated with gap
junction incompatibility to keratinocytes [31].
In general, low levels of Ecadherin may play an
important role in tumor progression, as occurs in
many carcinomas since cadherin loss is associated
with absence of differentiation and a more invasive
growth pattern [25, 38]. The suppressed Ecadherin
expression in carcinoma cells showed an increased
invasive potential in in vitro studies and the deep com
ponents of occasional melanoma showed substantial
reductions in cadherin expression [39, 40]. In cases
of malignant melanomas soluble Ecadherin levels in
serum were increased.
One possible explanation of the elevated serum
Ecadherin levels is that the damaged by invasive tumor
cells tissue releases Ecadherin. Another explanation is
that this soluble form may be degraded from Ecadhe
rin primarily expressed on tumor cells [41, 42]. Loss
of functional Ecadherin let melanocytes to escape
from the neighboring keratinocytes. In early melanoma
stages may still exist a basement membrane part, which
becomes irregular and dysfunctional [43].
Very important role in Ecadherin expression plays
the Snail protein. Overexpression of the Snail protein
reduces Ecadherin expression and increases the
metastatic potential of melanoma cells [44]. Sup
pression of the Snail protein expression reduces the
metastatic potential of melanoma cells [45]. Another
factor that can also lead to Ecadherin and Pcadherin
downregulation in human epidermal melanocytes,
is the exposure to UVBirradiation [46]. Dysfunc
tion of Ecadherin can be seen as change in cellular
localization, associated with high invasiveness and
metastasis of the overlying melanoma cells [47]. It
has been shown that the expression of membranous
Ecadherin remains in large amount during malignant
transformation in the radical growth phase of mela
noma and metastasis process 14]. Downregulation
of Ecadherin and/or its dysfunction is regarded to
be one of the earlier steps in the development of me
tastases in carcinomas, in general. This event may
also be one of the first steps in the development of
metastases in cutaneous melanomas cases [48]. It is
now well known that Snail leads to repression of the
cellcell adhesion molecule of Ecadherin. Ecadherin
gene is the first gene, which was described to be
targeted by Snail protein. Snail belongs to the Snail
superfamily of zincfinger transcription factors. Snail
superfamily is important in morphogenesis as well
[49]. In a recently published study it was reported an
important correlation between Ecadherin expression
and the depth of the primary tumor [50]. Ecadherin
expression is observed in cultured melanocytes and
nevus cells. Ecadherin is rarely found in early stages
of the melanocytic tumor and is lost in invasive and
metastatic melanoma cells in vitro [51]. Downregula
tion of Ecadherin may also downregulate genes in
volved in growth and metastasis possibly by affecting
the βcatenin/wnt signaling pathways [52]. It has also
been shown that Ecadherin gene is silenced by at
least two distinct mechanismsmethylation and trans
repression by the Snail protein [53]. All metastasizing
melanomas and their corresponding lymph node me
tastases may express membranous Ecadherin [47].
These results contradict the invasion suppressor role
described for Ecadherin in carcinomaderived cell
lines in vitro [54]. Another significant inverse relation
was detected between Ecadherin expression and
survival in some types of tumors [38, 55, 56]. Another
alternative way to observe the Ecadherin function
and its relation to the melanoma development, is
that by the reexpression of Ecadherin in Ecadherin
deficient melanoma cells. Adenoviral gene transfer
was used and surprisingly, Ecadherin transduction
inhibited Ncadherin expression in melanoma cells
[31]. The same was also proved by the use of full length
Ecadherin cDNA, which was transduced by the use of
an adenoviral vector to Ecadherin negative melanoma
cell lines. The result of Ecadherin restoration was re
duction of tumorigenicity and melanoma cells’ growth
retardation; thus, melanocytic phenotype was closer to
normal [35]. In threedimensional skin reconstructs it
was clearly shown that Ecadherin in melanoma cells
triggers also apoptosis [35]. In some experiments it
was revealed that full length Ecadherin transfection
downregulates endogenous Ncadherin expression
[57]. Although in general, there is a direct association
between decreased levels of Ecadherin expression
and tumorigenesis, surprisingly in a study an increase
of Ecadherin in a malignant lesion was found [32].
Furthermore, although non statistically significant, in
another study, it was reported that Ecadherin expres
sion tended to be preserved in melanoma [58]. In a skin
reconstruction model, ectopic adenoviralmediated
Ecadherin expression suppresses invasive capacity.
Specifically, inhibits some adhesion receptors such as
melanocyte cellular adhesion molecule or ανβ3 integrin
subunit [35]. It is shown that restoration of Ecadherin
expression leads to growth retardation and inhibition
of the invasiveness and metastasis in carcinoma cells
[59]. Several studies have proposed that Ecadherin
can act as a molecule that suppresses the invasive
ability [39, 60]. If exogenous Ecadherin cDNA is
introduced into epithelioid type cells, a partial tumori
genicity suppression is observed. This suggests that
Ecadherin can play an inhibiting role against tumor
growth [1]. Another role, which can play Ecadherin in
melanocytes apart from its tumor suppressor role, is
that of the prevention of naevus’ formation, as well as
melanomas growth and their metastasis [61].
N-CADHERIN IN MELANOMAS
Melanoma cells lose the capability of expressing
Ecadherin, but express Ncadherin at high levels
in vitro and in vivo [25, 62]. During the melanoma
development this change of cadherin subtypes gives
to melanoma cells the ability of direct interaction with
other cells that express Ncadherin. Fibroblasts and
vascular endothelial cells are some of them. As a result
190 Experimental Oncology 28, 187–193, 2006 (September)
tumor cells invasion, migration and tumorstroma cell
adhesion are affected. The described communica
tion between cells expressing Ncadherin is achieved
through gap junctions [31]. The role of Ncadherin in
melanoma metastasis is also suggested by the fact
that Ncadherin promotes migration of melanoma cells
over dermal fibroblasts [25]. High levels of Ncadherin
expression by the melanoma cells play role in the in
teractions with the Ncadherin positive fibroblasts and
endothelial cells [28]. It is obvious that the upregula
tion of Ncadherin endows melanoma cells with their
new adhesive properties [31]. Apart from adhesive
properties, loss of Ecadherin and gain of Ncadherin
expression during the melanoma progression provides
also new communication properties with Ncadherin
expressing neighboring melanoma cells or dermal
fibroblasts [63]. It seems that Ncadherin is the basic
cadherin expressed by the melanoblastic cells lines
in vitro. Very important is the amount of Ncadherin
produced, since it is associated with the transformation
stage. It has been shown with in vivo studies that the
pattern of expression of cadherins/catenins is dynamic
and associated not only with the stage but also with
the location of the cells [61]. It is suggested that the
switching of Ecadherin to Ncadherin provides the early
tumor with important motility and survival advantages;
however, endogenous Ecadherin is not affected by the
Ncadherin overexpression [64]. The role of Ncadherin
mediated cellcell adhesion could be characterized as
dual. It can be involved in the spreading of endothelial
process over transmigrated melanoma cells, but also in
the early event of transmigration due to the heterotypic
adhesion between endothelial and melanoma cells
[29]. Thus, Ncadherin plays a very important role in
the first stages of melanoma development by affecting
adhesion and communication properties, promoting
melanoma cells migration on fibroblasts and by the fact
that forced expression of Ncadherin in melanocytes
promotes migration in general. In investigated mela
noma cells lines, migration can be significantly inhibited
when the interaction between Ncadherin expressing
cells is blocked [65]. Blocking of Ncadherin synthesis
and inhibition of βcatenin signaling pathways, lead to
impairment of transendothelial migration of melanoma
cells [66].
P-CADHERIN IN MELANOMAS
A relatively few data is known regarding Pcadherin
expression in malignant melanomas. Pcadherin is
expressed on cells of the basal layers as well as on
the outer layers of skin appendage [1]. It is suggested
that Pcadherin is involved in the proliferating cell
compartment [67]. Pcadherin expression in malignant
melanomas is related to tumor proliferation and pro
gression supporting the hypothesis that Pcadherin,
as Ecadherin, is involved in invasion or metastasis [1].
The expression of Pcadherin in primary melanocytes
is well documented. More specifically, a truncated
variant of Pcadherin missing the transmembrane and
the cytoplasmic region expressed in melanoma cells
has been found [68]. It is believed, therefore, that
the soluble variant of Pcadherin blocks interaction
between cells, leading to migration and metastasis of
the malignant melanoma [69]. Cytoplasmic expres
sion of Pcadherin is associated with increasing tumor
thickness, level of invasion and reduced survival [69].
In cultures with Pcadherin negative cell lines, de novo
expression of Pcadherin led to promotion of cellcell
contact and aggregation [70].
VE-CADHERIN IN MELANOMAS
Another protein belonging to the cadherin super
family is the adhesive protein VEcadherin (vascular
endothelial cadherin). VEcadherin is expressed by
endothelial cells promoting cellcell interactions and
plays some role in angiogenesis and vascular permea
bility [71, 72]. VEcadherin is essential for both the
development and the maintenance of blood vessels
[73]. Aggressive human cutaneous and uveal mela
noma tumor cells express exclusively VEcadherin,
in contrast to poorly aggressive tumor cells [7]. The
expression of VEcadherin by aggressive melanoma
tumors is explained by their ability to mimic endothelial
cells and form consequently vasculogenic networks
[7]. This is possible under certain conditions, whereas
melanoma cells form tubular structures and patterned
networks [74]. VEcadherin disappeared from the
endothelial contact underneath the melanoma cell.
Migration begins with the small melanoma cells pene
trating the VEcadherin negative regions between
endothelial cells [29].
DYSADHERIN IN MELANOMAS
Recently it is reported the existence of a cancer
associated cell membrane glycoprotein named dys
adherin, with an antiadhesive role The expression of
this protein in cutaneous malignant melanoma is as
sociated with tumor aggressiveness and seems to be
a marker of poor prognosis [58]. Ecadherin function
and expression is downregulated by dysadherin. This
was proved by experiments where cells transfected
with dysadherin cDNA downregulated Ecadherin,
and promoted metastasis to the liver in an animal
model [75]. Dysadherin expression also was studied in
some malignancies in humans by our research group
[76–78]. Of course, further studies are needed to elu
cidate the role of dysadherin in human cancer cases
and particularly, in malignant melanomas.
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Experimental Oncology 28, 187–193, 2006 (September) 193
РОЛЬ КАДГЕРИН/КАТЕНИНОВОГО КОМПЛЕКСА ПРИ
ЗЛОКАЧЕСТВЕННОЙ МЕЛАНОМЕ
В обзоре обсуждается роль кадгерин/катенинового комплекса при злокачественной меланоме. Кадгерины представляют
собой суперсемейство адгезивных молекул, среди которых наиболее изучен эпителиальный кадгерин (Eкадгерин), выпол
няющий ключевую роль в норме и при инвазивном опухолевом росте и метастазировании. В ткани злокачественных меланом
уровень экспрессии Eкадгерина изменен, его снижение или отсутствие связано с инвазивным ростом и метастазированием
опухоли. При образовании злокачественных меланом в меланоцитах отмечают замену экспрессии Eкадерина на таковую
неврального кадгерина (Nкадгерина). Кроме того, коротко обсуждается роль плацентарного кадгерина (Pкадгерина),
эндотелиального кадгерина сосудов (VEкадерина) и недавно идентифицированного дисадгерина.
Ключевые слова: молекулы адгезии, кадгерин, катенин, дисадгерин, меланома.
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