دورية أكاديمية
SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis
| العنوان: | SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis |
|---|---|
| المؤلفون: | Pranzini, Erica, Pardella, Elisa, Muccillo, Livio, Leo, Angela, Nesi, Ilaria, Santi, Alice, Parri, Matteo, Zhang, Tong, Huerta Uribe, Alejandro, Lottini, Tiziano, Sabatino, Lina, Caselli, Anna, Arcangeli, Annarosa, Raugei, Giovanni, Colantuoni, Vittorio, Cirri, Paolo, Chiarugi, Paola, Maddocks, Oliver D. K., Paoli, Paolo, Taddei, Maria Letizia |
| بيانات النشر: | Elsevier (Cell Press) |
| سنة النشر: | 2022 |
| المجموعة: | University of Glasgow: Enlighten - Publications |
| الوصف: | 5-Fluorouracil (5-FU) is a key component of chemotherapy for colorectal cancer (CRC). 5-FU efficacy is established by intracellular levels of folate cofactors and DNA damage repair strategies. However, drug resistance still represents a major challenge. Here, we report that alterations in serine metabolism affect 5-FU sensitivity in in vitro and in vivo CRC models. In particular, 5-FU-resistant CRC cells display a strong serine dependency achieved either by upregulating endogenous serine synthesis or increasing exogenous serine uptake. Importantly, regardless of the serine feeder strategy, serine hydroxymethyltransferase-2 (SHMT2)-driven compartmentalization of one-carbon metabolism inside the mitochondria represents a specific adaptation of resistant cells to support purine biosynthesis and potentiate DNA damage response. Interfering with serine availability or affecting its mitochondrial metabolism revert 5-FU resistance. These data disclose a relevant mechanism of mitochondrial serine use supporting 5-FU resistance in CRC and provide perspectives for therapeutic approaches. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://eprints.gla.ac.uk/278241/1/278241.pdfTest; Pranzini, E. et al. (2022) SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis. Cell Reports , 40(7), 111233. (doi:10.1016/j.celrep.2022.111233 ) (PMID:35977477) |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2022.111233Test https://eprints.gla.ac.uk/278241Test/ https://eprints.gla.ac.uk/278241/1/278241.pdfTest |
| حقوق: | cc_by_nc_nd_4 |
| رقم الانضمام: | edsbas.E58FEFD2 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |