AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely u...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/19/4600 |
| _version_ | 1797480324849991680 |
|---|---|
| author | Jiakang Zhang Zhixuan Ren Dayong Zheng Zhenghui Song Junhao Lin Yue Luo Xiaopei Zou Yingying Pan Na Qi Aimin Li Xinhui Liu |
| author_facet | Jiakang Zhang Zhixuan Ren Dayong Zheng Zhenghui Song Junhao Lin Yue Luo Xiaopei Zou Yingying Pan Na Qi Aimin Li Xinhui Liu |
| author_sort | Jiakang Zhang |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely unknown. Actually, we found that AHSA1 was significantly upregulated in HCC tissues and cell lines and was notably correlated with the poor clinical characteristics and prognosis of HCC patients in this study. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated that AHSA1 promoted the proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) of HCC. Moreover, the mechanistic study indicated that AHSA1 recruited ERK1/2 and promoted the phosphorylation and inactivation of CALD1, while ERK1/2 phosphorylation inhibitor SCH772984 reversed the role of AHSA1 in the proliferation and EMT of HCC. Furthermore, we demonstrated that the knockdown of CALD1 reversed the inhibition of proliferation and EMT by knocking AHSA1 in HCC. We also illustrated a new molecular mechanism associated with AHSA1 in HCC that was independent of HSP90 and MEK1/2. In summary, AHSA1 may play an oncogenic role in HCC by regulating ERK/CALD1 axis and may serve as a novel therapeutic target for HCC. |
| first_indexed | 2024-03-09T21:58:36Z |
| format | Article |
| id | doaj.art-63ed6efd6531400388c627255d4511dc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:58:36Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-63ed6efd6531400388c627255d4511dc2023-11-23T19:53:30ZengMDPI AGCancers2072-66942022-09-011419460010.3390/cancers14194600AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular CarcinomaJiakang Zhang0Zhixuan Ren1Dayong Zheng2Zhenghui Song3Junhao Lin4Yue Luo5Xiaopei Zou6Yingying Pan7Na Qi8Aimin Li9Xinhui Liu10Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaCancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, ChinaHepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely unknown. Actually, we found that AHSA1 was significantly upregulated in HCC tissues and cell lines and was notably correlated with the poor clinical characteristics and prognosis of HCC patients in this study. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated that AHSA1 promoted the proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) of HCC. Moreover, the mechanistic study indicated that AHSA1 recruited ERK1/2 and promoted the phosphorylation and inactivation of CALD1, while ERK1/2 phosphorylation inhibitor SCH772984 reversed the role of AHSA1 in the proliferation and EMT of HCC. Furthermore, we demonstrated that the knockdown of CALD1 reversed the inhibition of proliferation and EMT by knocking AHSA1 in HCC. We also illustrated a new molecular mechanism associated with AHSA1 in HCC that was independent of HSP90 and MEK1/2. In summary, AHSA1 may play an oncogenic role in HCC by regulating ERK/CALD1 axis and may serve as a novel therapeutic target for HCC.https://www.mdpi.com/2072-6694/14/19/4600Hepatocellular carcinomaAHSA1ERK1/2CALD1 |
| spellingShingle | Jiakang Zhang Zhixuan Ren Dayong Zheng Zhenghui Song Junhao Lin Yue Luo Xiaopei Zou Yingying Pan Na Qi Aimin Li Xinhui Liu AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma Cancers Hepatocellular carcinoma AHSA1 ERK1/2 CALD1 |
| title | AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma |
| title_full | AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma |
| title_fullStr | AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma |
| title_full_unstemmed | AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma |
| title_short | AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma |
| title_sort | ahsa1 promotes proliferation and emt by regulating erk cald1 axis in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma AHSA1 ERK1/2 CALD1 |
| url | https://www.mdpi.com/2072-6694/14/19/4600 |
| work_keys_str_mv | AT jiakangzhang ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT zhixuanren ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT dayongzheng ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT zhenghuisong ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT junhaolin ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT yueluo ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT xiaopeizou ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT yingyingpan ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT naqi ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT aiminli ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma AT xinhuiliu ahsa1promotesproliferationandemtbyregulatingerkcald1axisinhepatocellularcarcinoma |