Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma

G Gremel; D Ryan; M Rafferty; F Lanigan; S Hegarty; M Lavelle; I Murphy; L Unwin; C Joyce; W Faller; E W McDermott; K Sheahan; F Ponten; W M Gallagher

doi:10.1038/bjc.2011.249

Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma

G Gremel
, D Ryan
, M Rafferty
, F Lanigan
, S Hegarty
, M Lavelle
, I Murphy
, L Unwin
, C Joyce
, W Faller
, E W McDermott
, K Sheahan
, F Ponten
, W M Gallagher

Research output: Contribution to journal › Article (Academic Journal) › peer-review

13 Citations (Scopus)

Abstract

BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer.

METHODS: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used.

RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity.

CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

Original language	English
Pages (from-to)	565-74
Number of pages	10
Journal	British Journal of Cancer
Volume	105
Issue number	4
DOIs	https://doi.org/10.1038/bjc.2011.249
Publication status	Published - 9 Aug 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Antigens, CD/metabolism
Apoptosis
Blotting, Western
Cadherins/metabolism
Cell Cycle
Cell Line, Tumor
Cell Survival
Cyclin-Dependent Kinase Inhibitor p21/metabolism
Disease-Free Survival
Down-Regulation
Electrophoresis, Polyacrylamide Gel
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
Homeodomain Proteins/metabolism
Humans
Immunohistochemistry
Inhibitor of Apoptosis Proteins/antagonists & inhibitors
Melanoma/genetics
Multivariate Analysis
Neoplasm Invasiveness
Predictive Value of Tests
Prognosis
Proportional Hazards Models
Protein Array Analysis
Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors
Signal Transduction
Skin Neoplasms/genetics
Spheroids, Cellular
Survival Analysis
Survivin
Up-Regulation

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@article{e9cb0e15415d41e3adca666d8d58397b,

title = "Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma",

abstract = "BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer.METHODS: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used.RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity.CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.",

keywords = "Antigens, CD/metabolism, Apoptosis, Blotting, Western, Cadherins/metabolism, Cell Cycle, Cell Line, Tumor, Cell Survival, Cyclin-Dependent Kinase Inhibitor p21/metabolism, Disease-Free Survival, Down-Regulation, Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Gene Expression Regulation, Neoplastic, Homeodomain Proteins/metabolism, Humans, Immunohistochemistry, Inhibitor of Apoptosis Proteins/antagonists \& inhibitors, Melanoma/genetics, Multivariate Analysis, Neoplasm Invasiveness, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Protein Array Analysis, Proto-Oncogene Proteins c-bcl-2/antagonists \& inhibitors, Signal Transduction, Skin Neoplasms/genetics, Spheroids, Cellular, Survival Analysis, Survivin, Up-Regulation",

author = "G Gremel and D Ryan and M Rafferty and F Lanigan and S Hegarty and M Lavelle and I Murphy and L Unwin and C Joyce and W Faller and McDermott, \{E W\} and K Sheahan and F Ponten and Gallagher, \{W M\}",

year = "2011",

month = aug,

day = "9",

doi = "10.1038/bjc.2011.249",

language = "English",

volume = "105",

pages = "565--74",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "4",

}

TY - JOUR

T1 - Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma

AU - Gremel, G

AU - Ryan, D

AU - Rafferty, M

AU - Lanigan, F

AU - Hegarty, S

AU - Lavelle, M

AU - Murphy, I

AU - Unwin, L

AU - Joyce, C

AU - Faller, W

AU - McDermott, E W

AU - Sheahan, K

AU - Ponten, F

AU - Gallagher, W M

PY - 2011/8/9

Y1 - 2011/8/9

N2 - BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer.METHODS: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used.RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity.CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

AB - BACKGROUND: The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer.METHODS: Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used.RESULTS: Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity.CONCLUSIONS: MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.

KW - Antigens, CD/metabolism

KW - Apoptosis

KW - Blotting, Western

KW - Cadherins/metabolism

KW - Cell Cycle

KW - Cell Line, Tumor

KW - Cell Survival

KW - Cyclin-Dependent Kinase Inhibitor p21/metabolism

KW - Disease-Free Survival

KW - Down-Regulation

KW - Electrophoresis, Polyacrylamide Gel

KW - Fluorescent Antibody Technique

KW - Gene Expression Regulation, Neoplastic

KW - Homeodomain Proteins/metabolism

KW - Humans

KW - Immunohistochemistry

KW - Inhibitor of Apoptosis Proteins/antagonists & inhibitors

KW - Melanoma/genetics

KW - Multivariate Analysis

KW - Neoplasm Invasiveness

KW - Predictive Value of Tests

KW - Prognosis

KW - Proportional Hazards Models

KW - Protein Array Analysis

KW - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors

KW - Signal Transduction

KW - Skin Neoplasms/genetics

KW - Spheroids, Cellular

KW - Survival Analysis

KW - Survivin

KW - Up-Regulation

U2 - 10.1038/bjc.2011.249

DO - 10.1038/bjc.2011.249

M3 - Article (Academic Journal)

C2 - 21730974

SN - 0007-0920

VL - 105

SP - 565

EP - 574

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 4

ER -

Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma

Abstract

UN SDGs

Keywords

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