Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year. The treatment effect in advanced HCC is still disappointing and prognosis of advanced HCC remains poor. Hence, to find more effective therapeutic targets to improve the treat...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/7/1843 |
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| author | Pei-Yi Chu Shiao-Lin Tung Kuo-Wang Tsai Fang-Ping Shen Shih-Hsuan Chan |
| author_facet | Pei-Yi Chu Shiao-Lin Tung Kuo-Wang Tsai Fang-Ping Shen Shih-Hsuan Chan |
| author_sort | Pei-Yi Chu |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year. The treatment effect in advanced HCC is still disappointing and prognosis of advanced HCC remains poor. Hence, to find more effective therapeutic targets to improve the treatment outcome of HCC is of urgent need. In this study, we reported the novel oncogenic function of SAAL1 (serum amyloid A-like 1) in HCC, which previously is considered as an inflammation-related gene. We found that SAAL1 was significantly upregulated in HCC tumor tissues when compared to the adjacent normal tissues and high expression of SAAL1 correlated with shorter overall survival in The Cancer Genome Atlas (TCGA) HCC database. Functionally, we showed that the depletion of SAAL1 significantly reduced cell proliferation, 3D colony formation, and migration/invasion abilities of HCC cancer cells. Furthermore, suppression of SAAL1 impaired the HGF/Met-driven Akt/mTOR phosphorylation cascade and increased the chemosensitivity of HCC cells to sorafenib and foretinib treatment. Our data indicated that SAAL1 plays an important role in HCC via mediating oncogenic HGF/Met-driven Akt/mTOR signaling and could serve as an independent prognostic marker, as well as a promising therapeutic target for HCC patients. |
| first_indexed | 2024-03-10T18:37:02Z |
| format | Article |
| id | doaj.art-e750676ef8e4441d85b834974d596642 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:37:02Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e750676ef8e4441d85b834974d5966422023-11-20T06:12:34ZengMDPI AGCancers2072-66942020-07-01127184310.3390/cancers12071843Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular CarcinomaPei-Yi Chu0Shiao-Lin Tung1Kuo-Wang Tsai2Fang-Ping Shen3Shih-Hsuan Chan4Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, TaiwanDepartment of Hematology and Oncology, Ton-Yen General Hospital, Hsinchu 302, TaiwanDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 235, TaiwanGraduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, TaiwanGraduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, Taichung 40402, TaiwanHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, affecting over 700,000 people per year. The treatment effect in advanced HCC is still disappointing and prognosis of advanced HCC remains poor. Hence, to find more effective therapeutic targets to improve the treatment outcome of HCC is of urgent need. In this study, we reported the novel oncogenic function of SAAL1 (serum amyloid A-like 1) in HCC, which previously is considered as an inflammation-related gene. We found that SAAL1 was significantly upregulated in HCC tumor tissues when compared to the adjacent normal tissues and high expression of SAAL1 correlated with shorter overall survival in The Cancer Genome Atlas (TCGA) HCC database. Functionally, we showed that the depletion of SAAL1 significantly reduced cell proliferation, 3D colony formation, and migration/invasion abilities of HCC cancer cells. Furthermore, suppression of SAAL1 impaired the HGF/Met-driven Akt/mTOR phosphorylation cascade and increased the chemosensitivity of HCC cells to sorafenib and foretinib treatment. Our data indicated that SAAL1 plays an important role in HCC via mediating oncogenic HGF/Met-driven Akt/mTOR signaling and could serve as an independent prognostic marker, as well as a promising therapeutic target for HCC patients.https://www.mdpi.com/2072-6694/12/7/1843HCCSAAL1HGFMet |
| spellingShingle | Pei-Yi Chu Shiao-Lin Tung Kuo-Wang Tsai Fang-Ping Shen Shih-Hsuan Chan Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma Cancers HCC SAAL1 HGF Met |
| title | Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma |
| title_full | Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma |
| title_fullStr | Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma |
| title_full_unstemmed | Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma |
| title_short | Identification of the Novel Oncogenic Role of SAAL1 and Its Therapeutic Potential in Hepatocellular Carcinoma |
| title_sort | identification of the novel oncogenic role of saal1 and its therapeutic potential in hepatocellular carcinoma |
| topic | HCC SAAL1 HGF Met |
| url | https://www.mdpi.com/2072-6694/12/7/1843 |
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