TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling
Abstract Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southern China, North Africa, and Southeast Asia. The translocase of the outer membrane (TOM) 40 is a transporter of mitochondrial proteins, and is involved in ovarian cancer cell growth. However, its role in the progression of NPC is...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2023-06-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-023-00721-3 |
| _version_ | 1797795597612220416 |
|---|---|
| author | Hong Ran Jin Zhang Xiaoxia Zeng Zhen Wang Peng Liu Chenglin Kang Shuqi Qiu Xianhai Zeng Peng Zhang |
| author_facet | Hong Ran Jin Zhang Xiaoxia Zeng Zhen Wang Peng Liu Chenglin Kang Shuqi Qiu Xianhai Zeng Peng Zhang |
| author_sort | Hong Ran |
| collection | DOAJ |
| description | Abstract Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southern China, North Africa, and Southeast Asia. The translocase of the outer membrane (TOM) 40 is a transporter of mitochondrial proteins, and is involved in ovarian cancer cell growth. However, its role in the progression of NPC is still unclear. We found that TOM40 levels were upregulated in NPC tissues and multiple NPC cell lines. In addition, high TOM40 expression in the tumor tissues was associated with poor overall survival and disease specific survival. TOM40 knockdown in the NPC cell lines inhibited their proliferation in vitro and in vivo. Furthermore, TOM40 silencing also increased intracellular production of reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Mechanistically, the anti-tumor effects of TOM40 silencing were dependent on the inhibition of AKT/mTOR signaling and activation of p53 signaling. To summarize, TOM40 mediates NPC progression through ROS-mediated AKT/mTOR and p53 signaling. Our findings highlight the potential of TOM40 as a therapeutic target for NPC. |
| first_indexed | 2024-03-13T03:21:22Z |
| format | Article |
| id | doaj.art-9d5e897a9965457db41ed8b122cfa6e4 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-03-13T03:21:22Z |
| publishDate | 2023-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-9d5e897a9965457db41ed8b122cfa6e42023-06-25T11:20:50ZengSpringerDiscover Oncology2730-60112023-06-0114111110.1007/s12672-023-00721-3TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signalingHong Ran0Jin Zhang1Xiaoxia Zeng2Zhen Wang3Peng Liu4Chenglin Kang5Shuqi Qiu6Xianhai Zeng7Peng Zhang8Department of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital & Shenzhen Key Laboratory of Otorhinolaryngology, Shenzhen Institute of OtorhinolaryngologyDepartment of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital & Shenzhen Key Laboratory of Otorhinolaryngology, Shenzhen Institute of OtorhinolaryngologyDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusDepartment of Graduate and Scientific Research, Zunyi Medical University Zhuhai CampusAbstract Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Southern China, North Africa, and Southeast Asia. The translocase of the outer membrane (TOM) 40 is a transporter of mitochondrial proteins, and is involved in ovarian cancer cell growth. However, its role in the progression of NPC is still unclear. We found that TOM40 levels were upregulated in NPC tissues and multiple NPC cell lines. In addition, high TOM40 expression in the tumor tissues was associated with poor overall survival and disease specific survival. TOM40 knockdown in the NPC cell lines inhibited their proliferation in vitro and in vivo. Furthermore, TOM40 silencing also increased intracellular production of reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Mechanistically, the anti-tumor effects of TOM40 silencing were dependent on the inhibition of AKT/mTOR signaling and activation of p53 signaling. To summarize, TOM40 mediates NPC progression through ROS-mediated AKT/mTOR and p53 signaling. Our findings highlight the potential of TOM40 as a therapeutic target for NPC.https://doi.org/10.1007/s12672-023-00721-3Nasopharyngeal carcinomaTOM40ROSAKTp53 |
| spellingShingle | Hong Ran Jin Zhang Xiaoxia Zeng Zhen Wang Peng Liu Chenglin Kang Shuqi Qiu Xianhai Zeng Peng Zhang TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling Discover Oncology Nasopharyngeal carcinoma TOM40 ROS AKT p53 |
| title | TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling |
| title_full | TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling |
| title_fullStr | TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling |
| title_full_unstemmed | TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling |
| title_short | TOM40 regulates the progression of nasopharyngeal carcinoma through ROS-mediated AKT/mTOR and p53 signaling |
| title_sort | tom40 regulates the progression of nasopharyngeal carcinoma through ros mediated akt mtor and p53 signaling |
| topic | Nasopharyngeal carcinoma TOM40 ROS AKT p53 |
| url | https://doi.org/10.1007/s12672-023-00721-3 |
| work_keys_str_mv | AT hongran tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT jinzhang tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT xiaoxiazeng tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT zhenwang tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT pengliu tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT chenglinkang tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT shuqiqiu tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT xianhaizeng tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling AT pengzhang tom40regulatestheprogressionofnasopharyngealcarcinomathroughrosmediatedaktmtorandp53signaling |