Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis and Prolongs Survival
| العنوان: | Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis and Prolongs Survival |
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| المؤلفون: | Yu Chan Chang, Michael Hsiao, Yi Fang Yang, Yuan Feng Lin, Ming Shyan Huang, Pei Jung Lu, Jean Chiou, Chia Yi Su, Chia-Ning Yang, Chih Jen Yang |
| المصدر: | Cancer Research. 79:4754-4766 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Lung Neoplasms, Adenocarcinoma of Lung, Antineoplastic Agents, Apoptosis, Mice, SCID, medicine.disease_cause, Metastasis, Small Molecule Libraries, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, In vivo, Fructose-Bisphosphate Aldolase, Tumor Cells, Cultured, Carcinoma, medicine, Animals, Humans, Protein Interaction Maps, Lung cancer, Cell Proliferation, Retrospective Studies, biology, Cell growth, business.industry, Aldolase A, Cancer, Prognosis, medicine.disease, Xenograft Model Antitumor Assays, Actins, Gene Expression Regulation, Neoplastic, Survival Rate, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Carcinoma, Large Cell, Female, Carcinogenesis, business |
| الوصف: | Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. Significance: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non–small lung cancer and that blocking this interaction could be an effective cancer treatment. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0146264884618f70cda58885bb83050bTest https://doi.org/10.1158/0008-5472.can-18-4080Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0146264884618f70cda58885bb83050b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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