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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Multidisciplinary Digital Publishing Institute
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/94059/ http://psasir.upm.edu.my/id/eprint/94059/1/94059.pdf |
| _version_ | 1848861906226380800 |
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| author | Kwan, Yuet Ping Teo, Melissa Hui Yen Lim, Jonathan Chee Woei Tan, Michelle Siying Rosellinny, Graciella Wahli, Walter Wang, Xiaomeng |
| 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 |
| building | UPM Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-15T13:08:34Z |
| format | Article |
| id | upm-94059 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T13:08:34Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-940592024-10-11T08:59:10Z 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 |
| 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 |
| title | 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_short | LRG1 promotes metastatic dissemination of melanoma through regulating EGFR/STAT3 signalling |
| title_sort | lrg1 promotes metastatic dissemination of melanoma through regulating egfr/stat3 signalling |
| url | http://psasir.upm.edu.my/id/eprint/94059/ http://psasir.upm.edu.my/id/eprint/94059/ http://psasir.upm.edu.my/id/eprint/94059/ http://psasir.upm.edu.my/id/eprint/94059/1/94059.pdf |