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LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling

Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the...

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Auteurs principaux: Kwan, Yuet Ping, Teo, Melissa Hui Yen, Lim, Jonathan Chee Woei, Tan, Michelle Siying, Rosellinny, Graciella, Wahli, Walter, Wang, Xiaomeng
Format: Article
Langue:English
Publié: Multidisciplinary Digital Publishing Institute 2021
Accès en ligne:http://psasir.upm.edu.my/id/eprint/94059/1/94059.pdf
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spelling oai:psasir.upm.edu.my:94059 http://psasir.upm.edu.my/id/eprint/94059/ LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling Kwan, Yuet Ping Teo, Melissa Hui Yen Lim, Jonathan Chee Woei Tan, Michelle Siying Rosellinny, Graciella Wahli, Walter Wang, Xiaomeng Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma. Multidisciplinary Digital Publishing Institute 2021-06-30 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/94059/1/94059.pdf Kwan, Yuet Ping and Teo, Melissa Hui Yen and Lim, Jonathan Chee Woei and Tan, Michelle Siying and Rosellinny, Graciella and Wahli, Walter and Wang, Xiaomeng (2021) LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling. Cancers, 13 (13). art. no. 3279. pp. 1-16. ISSN 2072-6694 https://www.mdpi.com/2072-6694/13/13/3279 10.3390/cancers13133279
institution UPM IR
collection UPM IR
language English
description Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma.
format Article
author Kwan, Yuet Ping
Teo, Melissa Hui Yen
Lim, Jonathan Chee Woei
Tan, Michelle Siying
Rosellinny, Graciella
Wahli, Walter
Wang, Xiaomeng
spellingShingle Kwan, Yuet Ping
Teo, Melissa Hui Yen
Lim, Jonathan Chee Woei
Tan, Michelle Siying
Rosellinny, Graciella
Wahli, Walter
Wang, Xiaomeng
LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
author_facet Kwan, Yuet Ping
Teo, Melissa Hui Yen
Lim, Jonathan Chee Woei
Tan, Michelle Siying
Rosellinny, Graciella
Wahli, Walter
Wang, Xiaomeng
author_sort Kwan, Yuet Ping
title LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
title_short LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
title_full LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
title_fullStr LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
title_full_unstemmed LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling
title_sort lrg1 promotes metastatic dissemination of melanoma through regulating egfr/stat3 signalling
publisher Multidisciplinary Digital Publishing Institute
publishDate 2021
url http://psasir.upm.edu.my/id/eprint/94059/1/94059.pdf
_version_ 1819300696408719360
score 13.4562235

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