Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway
Currently, exploring tumor-promoting or tumor-suppressing factors is a promising approach to find new targets for cancer therapy. In this context, through analysis of GSE datasets (GSE3189 and GSE112509), stress induced phosphoprotein 1 (STIP1) was found to be overexpressed in melanoma tissues compa...
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doaj-d8895b1ca0e94a018ac962dfa3b9943a2021-05-20T07:38:19ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-08-01116108962Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathwayXiaoyan Sun0Ningjia Cao1Liang Mu2Wei Cao3Department of Dermatology, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Xi’an, Shaanxi Province 710068, ChinaDepartment of Infectious Diseases, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Xi’an, Shaanxi Province 710068, ChinaUltrasound Diagnosis Center, Shaanxi Provincial People's Hospital,256 Youyi West Road, Xi’an, Shaanxi Province 710068, ChinaDepartment of Surgical Oncology, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Xi’an, Shaanxi Province 710068, China; Corresponding author.Currently, exploring tumor-promoting or tumor-suppressing factors is a promising approach to find new targets for cancer therapy. In this context, through analysis of GSE datasets (GSE3189 and GSE112509), stress induced phosphoprotein 1 (STIP1) was found to be overexpressed in melanoma tissues compared to benign skin nevi and normal skin tissues, respectively. High expression of STIP1 protein was further confirmed in our melanoma specimens. The survival data of skin cutaneous melanoma in TCGA database indicated that high STIP1 level predicted poor clinical outcomes of patients. Functionally, STIP1 knockdown significantly inhibited cell proliferation, migration and invasion, and induced apoptosis of A2058 cells in vitro. Additionally, STIP1 silencing prominently reduced lung metastasis of melanoma cells in vivo. Whereas, STIP1 overexpression facilitated the growth and metastasis of M14 cells. Intriguingly, STIP1 overexpression markedly increased Janus kinase 2 (JAK2) expression and activated JAK2/signal transducer and activator of transcription 3 (STAT3) pathway in M14 cells, while knockdown of STIP1 blocked JAK2/STAT3 pathway in A2058 cells. Importantly, JAK2 knockdown reversed STIP1-induced melanoma cell proliferation, migration and invasion. Thus, we revealed a novel mechanism underlying STIP1-induced melanoma progression by regulating JAK2/STAT3 pathway. This study might provide a new insight to understand the pathogenesis of melanoma and possibly contributed to development of therapeutic approaches for melanoma.http://www.sciencedirect.com/science/article/pii/S0753332219315501MelanomaSTIP1JAK2/STAT3 pathwayTumor growthMetastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoyan Sun Ningjia Cao Liang Mu Wei Cao |
spellingShingle |
Xiaoyan Sun Ningjia Cao Liang Mu Wei Cao Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway Biomedicine & Pharmacotherapy Melanoma STIP1 JAK2/STAT3 pathway Tumor growth Metastasis |
author_facet |
Xiaoyan Sun Ningjia Cao Liang Mu Wei Cao |
author_sort |
Xiaoyan Sun |
title |
Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway |
title_short |
Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway |
title_full |
Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway |
title_fullStr |
Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway |
title_full_unstemmed |
Stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating JAK2/STAT3 pathway |
title_sort |
stress induced phosphoprotein 1 promotes tumor growth and metastasis of melanoma via modulating jak2/stat3 pathway |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-08-01 |
description |
Currently, exploring tumor-promoting or tumor-suppressing factors is a promising approach to find new targets for cancer therapy. In this context, through analysis of GSE datasets (GSE3189 and GSE112509), stress induced phosphoprotein 1 (STIP1) was found to be overexpressed in melanoma tissues compared to benign skin nevi and normal skin tissues, respectively. High expression of STIP1 protein was further confirmed in our melanoma specimens. The survival data of skin cutaneous melanoma in TCGA database indicated that high STIP1 level predicted poor clinical outcomes of patients. Functionally, STIP1 knockdown significantly inhibited cell proliferation, migration and invasion, and induced apoptosis of A2058 cells in vitro. Additionally, STIP1 silencing prominently reduced lung metastasis of melanoma cells in vivo. Whereas, STIP1 overexpression facilitated the growth and metastasis of M14 cells. Intriguingly, STIP1 overexpression markedly increased Janus kinase 2 (JAK2) expression and activated JAK2/signal transducer and activator of transcription 3 (STAT3) pathway in M14 cells, while knockdown of STIP1 blocked JAK2/STAT3 pathway in A2058 cells. Importantly, JAK2 knockdown reversed STIP1-induced melanoma cell proliferation, migration and invasion. Thus, we revealed a novel mechanism underlying STIP1-induced melanoma progression by regulating JAK2/STAT3 pathway. This study might provide a new insight to understand the pathogenesis of melanoma and possibly contributed to development of therapeutic approaches for melanoma. |
topic |
Melanoma STIP1 JAK2/STAT3 pathway Tumor growth Metastasis |
url |
http://www.sciencedirect.com/science/article/pii/S0753332219315501 |
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