Ji Young Kang, Hyeijin Cho, Minchan Gil, Haeryung Lee, Soochul Park, Kyung Eun Kim
{"title":"新型预后标志物 SPOCK2 可调控黑色素瘤的肿瘤进展。","authors":"Ji Young Kang, Hyeijin Cho, Minchan Gil, Haeryung Lee, Soochul Park, Kyung Eun Kim","doi":"10.1111/exd.15092","DOIUrl":null,"url":null,"abstract":"<p>Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that <i>SPOCK2</i> plays important roles in the progression of various human cancers; however, the role of <i>SPOCK2</i> in melanoma remains unknown. Therefore, this study investigated the roles of <i>SPOCK2</i> and the related mechanisms in melanoma progression. To evaluate the clinical significance of <i>SPOCK2</i> expression in patients with melanoma, we analysed the association between <i>SPOCK2</i> expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of <i>Spock2</i> in melanoma progression in vitro and in vivo, we knocked down <i>Spock2</i> in the B16F10 melanoma cell line. High <i>SPOCK2</i> levels were positively associated with good prognosis and long survival rate of patients with melanoma. <i>Spock2</i> knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, <i>Spock2</i> downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in <i>Spock2</i> knockdown cells. Therefore, <i>Spock2</i> could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, <i>Spock2</i> knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that <i>SPOCK2</i> plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The novel prognostic marker SPOCK2 regulates tumour progression in melanoma\",\"authors\":\"Ji Young Kang, Hyeijin Cho, Minchan Gil, Haeryung Lee, Soochul Park, Kyung Eun Kim\",\"doi\":\"10.1111/exd.15092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that <i>SPOCK2</i> plays important roles in the progression of various human cancers; however, the role of <i>SPOCK2</i> in melanoma remains unknown. Therefore, this study investigated the roles of <i>SPOCK2</i> and the related mechanisms in melanoma progression. To evaluate the clinical significance of <i>SPOCK2</i> expression in patients with melanoma, we analysed the association between <i>SPOCK2</i> expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of <i>Spock2</i> in melanoma progression in vitro and in vivo, we knocked down <i>Spock2</i> in the B16F10 melanoma cell line. High <i>SPOCK2</i> levels were positively associated with good prognosis and long survival rate of patients with melanoma. <i>Spock2</i> knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, <i>Spock2</i> downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in <i>Spock2</i> knockdown cells. Therefore, <i>Spock2</i> could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, <i>Spock2</i> knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that <i>SPOCK2</i> plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.</p>\",\"PeriodicalId\":12243,\"journal\":{\"name\":\"Experimental Dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/exd.15092\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Dermatology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/exd.15092","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
The novel prognostic marker SPOCK2 regulates tumour progression in melanoma
Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.
期刊介绍:
Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.