CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
| العنوان: | CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer |
|---|---|
| المؤلفون: | Nataliia Petruk, Malin Åkerfelt, Gennady G. Yegutkin, Jesse Mattsson, Sanni Tuominen, Arja Jukkola, Johanna Tuomela, Jouko Sandholm, Katri S. Selander, Matthias Nees |
| المساهمون: | Tampere University, Department of Oncology, Clinical Medicine |
| المصدر: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| بيانات النشر: | Nature Publishing Group UK, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adenosine monophosphate, Epithelial-Mesenchymal Transition, Lung Neoplasms, Science, Cell, 3122 Cancers, Mammary Neoplasms, Animal, Triple Negative Breast Neoplasms, GPI-Linked Proteins, Article, Small hairpin RNA, chemistry.chemical_compound, Mice, Breast cancer, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Cell migration, Epithelial–mesenchymal transition, Neoplasm Metastasis, 5'-Nucleotidase, Mice, Inbred BALB C, Multidisciplinary, Adenosine, Neoplasm Proteins, medicine.anatomical_structure, chemistry, Tumor progression, Cancer cell, Cancer research, Medicine, Female, medicine.drug |
| الوصف: | CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition. |
| وصف الملف: | fulltext |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0adec61e67ea321b05fbc366bc9163aaTest http://europepmc.org/articles/PMC7966763Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0adec61e67ea321b05fbc366bc9163aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
|---|