Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies
The cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and contributes to metabolic reprogramming, thus promoting...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/1/108 |
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| author | Jolanda Magri Alessandro Gasparetto Laura Conti Enzo Calautti Chiara Cossu Roberto Ruiu Giuseppina Barutello Federica Cavallo |
| author_facet | Jolanda Magri Alessandro Gasparetto Laura Conti Enzo Calautti Chiara Cossu Roberto Ruiu Giuseppina Barutello Federica Cavallo |
| author_sort | Jolanda Magri |
| collection | DOAJ |
| description | The cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and contributes to metabolic reprogramming, thus promoting tumor progression and chemoresistance. Moreover, xCT is overexpressed in cancer stem cells. These features render xCT a promising target for cancer therapy, as has been widely reported in the literature and in our work on its immunotargeting. Interestingly, studies on the TP53 gene have revealed that both wild-type and mutant p53 induce the post-transcriptional down modulation of xCT, contributing to ferroptosis. Moreover, APR-246, a small molecule drug that can restore wild-type p53 function in cancer cells, has been described as an indirect modulator of xCT expression in tumors with mutant p53 accumulation, and is thus a promising drug to use in combination with xCT inhibition. This review summarizes the current knowledge of xCT and its regulation by p53, with a focus on the crosstalk of these two molecules in ferroptosis, and also considers some possible combinatorial strategies that can make use of APR-246 treatment in combination with anti-xCT immunotargeting. |
| first_indexed | 2024-03-09T05:32:01Z |
| format | Article |
| id | doaj.art-26bf418ef18342478b6b709c47443fdb |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:32:01Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-26bf418ef18342478b6b709c47443fdb2023-12-03T12:31:15ZengMDPI AGCells2073-44092021-01-0110110810.3390/cells10010108Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor StrategiesJolanda Magri0Alessandro Gasparetto1Laura Conti2Enzo Calautti3Chiara Cossu4Roberto Ruiu5Giuseppina Barutello6Federica Cavallo7Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, ItalyThe cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and contributes to metabolic reprogramming, thus promoting tumor progression and chemoresistance. Moreover, xCT is overexpressed in cancer stem cells. These features render xCT a promising target for cancer therapy, as has been widely reported in the literature and in our work on its immunotargeting. Interestingly, studies on the TP53 gene have revealed that both wild-type and mutant p53 induce the post-transcriptional down modulation of xCT, contributing to ferroptosis. Moreover, APR-246, a small molecule drug that can restore wild-type p53 function in cancer cells, has been described as an indirect modulator of xCT expression in tumors with mutant p53 accumulation, and is thus a promising drug to use in combination with xCT inhibition. This review summarizes the current knowledge of xCT and its regulation by p53, with a focus on the crosstalk of these two molecules in ferroptosis, and also considers some possible combinatorial strategies that can make use of APR-246 treatment in combination with anti-xCT immunotargeting.https://www.mdpi.com/2073-4409/10/1/108xCTp53PRIMA-1APR-246breast cancer |
| spellingShingle | Jolanda Magri Alessandro Gasparetto Laura Conti Enzo Calautti Chiara Cossu Roberto Ruiu Giuseppina Barutello Federica Cavallo Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies Cells xCT p53 PRIMA-1 APR-246 breast cancer |
| title | Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies |
| title_full | Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies |
| title_fullStr | Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies |
| title_full_unstemmed | Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies |
| title_short | Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies |
| title_sort | tumor associated antigen xct and mutant p53 as molecular targets for new combinatorial antitumor strategies |
| topic | xCT p53 PRIMA-1 APR-246 breast cancer |
| url | https://www.mdpi.com/2073-4409/10/1/108 |
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