Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma
Abstract The nuclear receptor liver receptor homolog 1 (LRH1)/NR5A2 is aberrantly expressed in diverse cancer types, including liver and lung cancers. Since we previously showed that excessive phosphorylation of human LRH1 at S510 (hLRH1pS510-high) is predictable of hepatocellular carcinoma recurren...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14160-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849311110343163904 |
|---|---|
| author | Hayato Mine Kotaro Sugimoto Makoto Kobayashi Hironori Takagi Naoyuki Okabe Satoshi Muto Yasuyuki Kobayashi Yuko Hashimoto Hiroyuki Suzuki Hideki Chiba |
| author_facet | Hayato Mine Kotaro Sugimoto Makoto Kobayashi Hironori Takagi Naoyuki Okabe Satoshi Muto Yasuyuki Kobayashi Yuko Hashimoto Hiroyuki Suzuki Hideki Chiba |
| author_sort | Hayato Mine |
| collection | DOAJ |
| description | Abstract The nuclear receptor liver receptor homolog 1 (LRH1)/NR5A2 is aberrantly expressed in diverse cancer types, including liver and lung cancers. Since we previously showed that excessive phosphorylation of human LRH1 at S510 (hLRH1pS510-high) is predictable of hepatocellular carcinoma recurrence, we here clarified the clinicopathological and biological significance of hLRH1pS510-high in lung cancer. By immunohistochemistry using an anti-hLRH1pS510 monoclonal antibody, we evaluated the hLRH1pS510 signals in 151 and 150 cases of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, respectively, and performed clinicopathological analysis. hLRH1pS510 was localized in the nucleus of tumor cells in LUAD and LUSC tissues with different intensity and proportions among the patients. Of note, the strong hLRH1pS510 signal was occasionally detectable in LUAD and LUSC cells at the expanding tumor edges. A semi-quantitative analysis revealed that 28 (18.4%) and 36 (24.0%) of LUAD and LUSC cases, respectively, exhibited hLRH1pS510-high. Kaplan-Meier plots showed significant differences in the disease-free survival (DFS) between the hLRH1pS510-high and hLRH1pS510-low groups in LUSC, but not in LUAD patients. hLRH1pS510-high was also significantly correlated with recurrence in LUSC patients. Additionally, by multivariate analysis, hLRH1pS510-high represented an independent biomarker for the DFS of LUSC patients. Furthermore, the impact of hLRH1pS510 on the viability of LUSC cells was evaluated by comparing phenotypes among two distinct LUSC cell lines expressing wild-type LRH1, LRH1S510A, and LRH1S510E. Consequently, we demonstrated that phosphorylation of hLRH1S510 accelerates the viability of LUSC cells. Thus, hLRH1pS510 is attractive not only as the predictive biomarker for LUSC but also as the potential therapeutic target. |
| format | Article |
| id | doaj-art-77f987f3e71a4a3dac58dda2072faefb |
| institution | Kabale University |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-77f987f3e71a4a3dac58dda2072faefb2025-08-20T03:53:32ZengBMCBMC Cancer1471-24072025-04-0125111210.1186/s12885-025-14160-6Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinomaHayato Mine0Kotaro Sugimoto1Makoto Kobayashi2Hironori Takagi3Naoyuki Okabe4Satoshi Muto5Yasuyuki Kobayashi6Yuko Hashimoto7Hiroyuki Suzuki8Hideki Chiba9Department of Basic Pathology, Fukushima Medical University School of MedicineDepartment of Basic Pathology, Fukushima Medical University School of MedicineDepartment of Basic Pathology, Fukushima Medical University School of MedicineDepartment of Chest Surgery, Fukushima Medical University School of MedicineDepartment of Chest Surgery, Fukushima Medical University School of MedicineDepartment of Chest Surgery, Fukushima Medical University School of MedicineDepartment of Diagnostic Pathology, Fukushima Medical University School of MedicineDepartment of Diagnostic Pathology, Fukushima Medical University School of MedicineDepartment of Chest Surgery, Fukushima Medical University School of MedicineDepartment of Basic Pathology, Fukushima Medical University School of MedicineAbstract The nuclear receptor liver receptor homolog 1 (LRH1)/NR5A2 is aberrantly expressed in diverse cancer types, including liver and lung cancers. Since we previously showed that excessive phosphorylation of human LRH1 at S510 (hLRH1pS510-high) is predictable of hepatocellular carcinoma recurrence, we here clarified the clinicopathological and biological significance of hLRH1pS510-high in lung cancer. By immunohistochemistry using an anti-hLRH1pS510 monoclonal antibody, we evaluated the hLRH1pS510 signals in 151 and 150 cases of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, respectively, and performed clinicopathological analysis. hLRH1pS510 was localized in the nucleus of tumor cells in LUAD and LUSC tissues with different intensity and proportions among the patients. Of note, the strong hLRH1pS510 signal was occasionally detectable in LUAD and LUSC cells at the expanding tumor edges. A semi-quantitative analysis revealed that 28 (18.4%) and 36 (24.0%) of LUAD and LUSC cases, respectively, exhibited hLRH1pS510-high. Kaplan-Meier plots showed significant differences in the disease-free survival (DFS) between the hLRH1pS510-high and hLRH1pS510-low groups in LUSC, but not in LUAD patients. hLRH1pS510-high was also significantly correlated with recurrence in LUSC patients. Additionally, by multivariate analysis, hLRH1pS510-high represented an independent biomarker for the DFS of LUSC patients. Furthermore, the impact of hLRH1pS510 on the viability of LUSC cells was evaluated by comparing phenotypes among two distinct LUSC cell lines expressing wild-type LRH1, LRH1S510A, and LRH1S510E. Consequently, we demonstrated that phosphorylation of hLRH1S510 accelerates the viability of LUSC cells. Thus, hLRH1pS510 is attractive not only as the predictive biomarker for LUSC but also as the potential therapeutic target.https://doi.org/10.1186/s12885-025-14160-6Nuclear receptorNR5A2Liver receptor homolog 1Lung cancerLung adenocarcinomaBiomarker |
| spellingShingle | Hayato Mine Kotaro Sugimoto Makoto Kobayashi Hironori Takagi Naoyuki Okabe Satoshi Muto Yasuyuki Kobayashi Yuko Hashimoto Hiroyuki Suzuki Hideki Chiba Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma BMC Cancer Nuclear receptor NR5A2 Liver receptor homolog 1 Lung cancer Lung adenocarcinoma Biomarker |
| title | Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| title_full | Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| title_fullStr | Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| title_full_unstemmed | Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| title_short | Abnormal phosphorylation of human LRH1 at Ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| title_sort | abnormal phosphorylation of human lrh1 at ser510 predicts poor prognosis and promotes cell viability in lung squamous cell carcinoma |
| topic | Nuclear receptor NR5A2 Liver receptor homolog 1 Lung cancer Lung adenocarcinoma Biomarker |
| url | https://doi.org/10.1186/s12885-025-14160-6 |
| work_keys_str_mv | AT hayatomine abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT kotarosugimoto abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT makotokobayashi abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT hironoritakagi abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT naoyukiokabe abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT satoshimuto abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT yasuyukikobayashi abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT yukohashimoto abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT hiroyukisuzuki abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma AT hidekichiba abnormalphosphorylationofhumanlrh1atser510predictspoorprognosisandpromotescellviabilityinlungsquamouscellcarcinoma |