SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination
Abstract Gastric cancer peritoneal dissemination (GCPD) has been recognized as the most common form of metastasis in advanced gastric cancer (GC), and the survival is pessimistic. The injury of mesothelial cells plays an important role in GCPD. However, its molecular mechanism is not entirely clear....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2041 |
| _version_ | 1797387190815162368 |
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| author | Songcheng Yin Zhifeng Miao Yuen Tan Pengliang Wang Xiaoyu Xu Chao Zhang Wenbin Hou Jinyu Huang Huimian Xu |
| author_facet | Songcheng Yin Zhifeng Miao Yuen Tan Pengliang Wang Xiaoyu Xu Chao Zhang Wenbin Hou Jinyu Huang Huimian Xu |
| author_sort | Songcheng Yin |
| collection | DOAJ |
| description | Abstract Gastric cancer peritoneal dissemination (GCPD) has been recognized as the most common form of metastasis in advanced gastric cancer (GC), and the survival is pessimistic. The injury of mesothelial cells plays an important role in GCPD. However, its molecular mechanism is not entirely clear. Here, we focused on the sphingosine kinase 1 (SPHK1) in human peritoneal mesothelial cells (HPMCs) which regulates HPMCs autophagy in GCPD progression. Initially, we analyzed SPHK1 expression immunohistochemically in 120 GC peritoneal tissues, and found high SPHK1 expression to be significantly associated with LC3B expression and peritoneal recurrence, leading to poor prognosis. Using a coculture system, we observed that GC cells promoted HPMCs autophagy and this process was inhibited by blocking TGF‐β1 secreted from GC cells. Autophagic HPMCs induced adhesion and invasion of GC cells. We also confirmed that knockdown of SPHK1 expression in HPMCs inhibited TGF‐β1‐induced autophagy. In addition, SPHK1‐driven autophagy of HPMCs accelerated GC cells occurrence of GCPD in vitro and in vivo. Moreover, we explored the relationship between autophagy and fibrosis in HPMCs, observing that overexpression of SPHK1 induced HPMCs fibrosis, while the inhibition of autophagy weakened HPMCs fibrosis. Taken together, our results provided new insights for understanding the mechanisms of GCPD and established SPHK1 as a novel target for GCPD. |
| first_indexed | 2024-03-08T22:20:17Z |
| format | Article |
| id | doaj.art-683020839f794cb0b2808f0431c77638 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T22:20:17Z |
| publishDate | 2019-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-683020839f794cb0b2808f0431c776382023-12-18T12:55:50ZengWileyCancer Medicine2045-76342019-04-01841731174310.1002/cam4.2041SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal disseminationSongcheng Yin0Zhifeng Miao1Yuen Tan2Pengliang Wang3Xiaoyu Xu4Chao Zhang5Wenbin Hou6Jinyu Huang7Huimian Xu8Department of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Gynecology The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaDepartment of Surgical Oncology First Affiliated Hospital of China Medical University Shenyang ChinaAbstract Gastric cancer peritoneal dissemination (GCPD) has been recognized as the most common form of metastasis in advanced gastric cancer (GC), and the survival is pessimistic. The injury of mesothelial cells plays an important role in GCPD. However, its molecular mechanism is not entirely clear. Here, we focused on the sphingosine kinase 1 (SPHK1) in human peritoneal mesothelial cells (HPMCs) which regulates HPMCs autophagy in GCPD progression. Initially, we analyzed SPHK1 expression immunohistochemically in 120 GC peritoneal tissues, and found high SPHK1 expression to be significantly associated with LC3B expression and peritoneal recurrence, leading to poor prognosis. Using a coculture system, we observed that GC cells promoted HPMCs autophagy and this process was inhibited by blocking TGF‐β1 secreted from GC cells. Autophagic HPMCs induced adhesion and invasion of GC cells. We also confirmed that knockdown of SPHK1 expression in HPMCs inhibited TGF‐β1‐induced autophagy. In addition, SPHK1‐driven autophagy of HPMCs accelerated GC cells occurrence of GCPD in vitro and in vivo. Moreover, we explored the relationship between autophagy and fibrosis in HPMCs, observing that overexpression of SPHK1 induced HPMCs fibrosis, while the inhibition of autophagy weakened HPMCs fibrosis. Taken together, our results provided new insights for understanding the mechanisms of GCPD and established SPHK1 as a novel target for GCPD.https://doi.org/10.1002/cam4.2041autophagygastric cancer peritoneal disseminationmesothelial cellSPHK1 |
| spellingShingle | Songcheng Yin Zhifeng Miao Yuen Tan Pengliang Wang Xiaoyu Xu Chao Zhang Wenbin Hou Jinyu Huang Huimian Xu SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination Cancer Medicine autophagy gastric cancer peritoneal dissemination mesothelial cell SPHK1 |
| title | SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| title_full | SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| title_fullStr | SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| title_full_unstemmed | SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| title_short | SPHK1‐induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| title_sort | sphk1 induced autophagy in peritoneal mesothelial cell enhances gastric cancer peritoneal dissemination |
| topic | autophagy gastric cancer peritoneal dissemination mesothelial cell SPHK1 |
| url | https://doi.org/10.1002/cam4.2041 |
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