LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling
| Autor: | Yuet Ping Kwan, Michelle Siying Tan, Xiaomeng Wang, Walter Wahli, Jonathan Chee Woei Lim, Graciella Rosellinny, Melissa Hui Yen Teo |
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| Přispěvatelé: | Duke-NUS Medical School [Singapore], Singapore Eye Research Institute [Singapore] (SERI), Universiti Putra Malaysia, National University of Singapore (NUS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Agency for science, technology and research [Singapore] (A*STAR), This project was supported by the MOE Academic Research Fund Tier 2 (MOE2014-T2-1036) to X.W. andW.W., the Duke-NUS Start-Up Grant to X.W. and the Singapore National Medical Research Council DYNAMO NMRC/OFLCG/001/2017 and TAPP NMRC/OFLCG/004/2018 to X.W., and the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-up Grant to W.W., Lee Kong Chian School of Medicine (LKCMedicine) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
leucine-rich α-2-glycoprotein-1 Cancer Research Angiogenesis [SDV]Life Sciences [q-bio] EGFR Cell Article Metastasis STAT3 03 medical and health sciences 0302 clinical medicine leucine-rich alpha-2-glycoprotein-1 medicine melanoma metastasis Medicine [Science] Melanoma neoplasms RC254-282 Cell growth business.industry Leucine-Rich α-2-Glycoprotein-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell migration medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology LRG1 030220 oncology & carcinogenesis Cancer research Skin cancer business |
| Zdroj: | Cancers, Vol 13, Iss 3279, p 3279 (2021) Cancers Volume 13 Issue 13 Cancers, MDPI, 2021, 13 (13), ⟨10.3390/cancers13133279⟩ |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13133279⟩ |
| Popis: | 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. Ministry of Education (MOE) National Medical Research Council (NMRC) Published version This project was supported by the MOE Academic Research Fund Tier 2 (MOE2014-T2-1- 036) to X.W. and W.W., the Duke-NUS Start-Up Grant to X.W. and the Singapore National Medical Research Council DYNAMO NMRC/OFLCG/001/2017 and TAPP NMRC/OFLCG/004/2018 to X.W., and the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-up Grant to W.W. |
| Databáze: | OpenAIRE |
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