Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation
Epithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2022-01-01
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| Series: | Open Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/med-2022-0422 |
| _version_ | 1828381297093902336 |
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| author | Dai Lan Wang Chen Wang Wenjing Song Keqi Ye Taiyang Zhu Jie Di Wen |
| author_facet | Dai Lan Wang Chen Wang Wenjing Song Keqi Ye Taiyang Zhu Jie Di Wen |
| author_sort | Dai Lan |
| collection | DOAJ |
| description | Epithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence that adipocytes induce the activation of sphingosine kinase (SphK) 2 in EOC, which represents a novel pathway that mediates the adipocyte-induced EOC growth. SphK2 inhibition in EOC cells led to a remarkable inhibition of the adipocyte-induced cell proliferation. Moreover, the adipocyte-induced SphK2 activation in EOC cells was extracellular signal-regulated protein kinases (ERK) dependent. Furthermore, silencing SphK2 in EOC significantly inhibited the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial players in EOC growth. Collectively, the current study unraveled a previously unrecognized role of SphK2 in the adipocyte-induced growth-promoting action in EOC, suggesting a novel target for EOC treatment. |
| first_indexed | 2024-12-10T04:12:24Z |
| format | Article |
| id | doaj.art-7bbb10b80b06482a9e7c1fafa4de8848 |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-12-10T04:12:24Z |
| publishDate | 2022-01-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Medicine |
| spelling | doaj.art-7bbb10b80b06482a9e7c1fafa4de88482022-12-22T02:02:41ZengDe GruyterOpen Medicine2391-54632022-01-0117122923810.1515/med-2022-0422Activation of SphK2 contributes to adipocyte-induced EOC cell proliferationDai Lan0Wang Chen1Wang Wenjing2Song Keqi3Ye Taiyang4Zhu Jie5Di Wen6Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaDepartment of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, ChinaEpithelial ovarian cancer (EOC) is the leading cause of deaths due to cancer in women. Adipocytes have been suggested to play a key role in the stimulation of EOC growth. However, the mechanisms underlying the adipocyte-induced EOC proliferation remain undefined. Here, we provide the first evidence that adipocytes induce the activation of sphingosine kinase (SphK) 2 in EOC, which represents a novel pathway that mediates the adipocyte-induced EOC growth. SphK2 inhibition in EOC cells led to a remarkable inhibition of the adipocyte-induced cell proliferation. Moreover, the adipocyte-induced SphK2 activation in EOC cells was extracellular signal-regulated protein kinases (ERK) dependent. Furthermore, silencing SphK2 in EOC significantly inhibited the adipocyte-induced expression of phospho-ERK and c-Myc, two crucial players in EOC growth. Collectively, the current study unraveled a previously unrecognized role of SphK2 in the adipocyte-induced growth-promoting action in EOC, suggesting a novel target for EOC treatment.https://doi.org/10.1515/med-2022-0422epithelial ovarian canceradipocytessphingosine kinase 2proliferation |
| spellingShingle | Dai Lan Wang Chen Wang Wenjing Song Keqi Ye Taiyang Zhu Jie Di Wen Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation Open Medicine epithelial ovarian cancer adipocytes sphingosine kinase 2 proliferation |
| title | Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation |
| title_full | Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation |
| title_fullStr | Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation |
| title_full_unstemmed | Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation |
| title_short | Activation of SphK2 contributes to adipocyte-induced EOC cell proliferation |
| title_sort | activation of sphk2 contributes to adipocyte induced eoc cell proliferation |
| topic | epithelial ovarian cancer adipocytes sphingosine kinase 2 proliferation |
| url | https://doi.org/10.1515/med-2022-0422 |
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