Team
RNA Biology, Signalling and Cancer (U1278)
Presentation
RNA BIOLOGY, SIGNALING AND CANCER
Our team focuses on the role of RNA regulations and RNA-binding proteins in cancer biology and anticancer therapy.
We study co-/post-transcriptional gene regulation (most notably intronic polyadenylation and translation) and RNA-binding proteins (RBPs, both canonical and non-canonical) in several aspects of cancer biology and anticancer therapies (genome instability and genotoxic chemotherapy; oncogenic signaling pathways and targeted therapies; T lymphocytes and cancer) and in several cancer types (cutaneous melanoma, breast cancer, acute T lymphoblastic leukemia, non-small cell lung cancer).
To tackle these issues, we use a combination of approaches: biochemical analyses of RNA, proteins and their interactions; genome-wide analyses of RNA regulations (RNA-seq, 3’seq, polysome profiling) and RNA-protein interactions (iCLIP); analyses of cancer cell phenotypes in cell culture; tumor biology in vivo and patients tumors.
Ongoing projects
Axis 1: Response to DNA damage and anticancer therapies.
1.1- Role of intronic polyadenylation (axis led by M. Dutertre).
1.2- Interaction between DNA-damage response proteins and RNA.
Axis 2: Tumor-intrinsic mechanisms of resistance to targeted therapies.
2.1- Dynamic reprogramming of mRNA translation in drug-tolerant cancer cells.
2.2- Direct interaction between MAPK signaling proteins and RNAs.
Axis 3: Crosstalk between tumor cells and their environment.
3.1- T cell receptor-dependent gene regulation in acute T lymphoblastic leukemia.
3.2- Immune-dependent post-transcriptional gene regulation in melanoma.
Main publications since 2014
(*co-corresponding authors, #co-first authors)
Sfaxi R, Biswas B, Boldina G, Cadix M, Servant N, Chen H, Larson DR, Dutertre M, Robert C, Vagner S. Post-transcriptional polyadenylation site cleavage maintains 3'-end processing upon DNA damage. EMBO J. 2023 Apr 3;42(7):e112358. doi: 10.15252/embj.2022112358. Epub 2023 Feb 10. PMID: 36762421
Chakraborty A, Cadix M, Relier S, Taricco N, Alaeitabar T, Devaux A, Labbé CM, Martineau S, Heneman-Masurel A, Gestraud P, Inga A, Servant N, Vagner S, Dutertre M (2022). Compartment-specific and ELAVL1-coordinated regulation of intronic polyadenylation isoforms by doxorubicin. Genome Res. 32(7):1271–84. doi: 10.1101/gr.276192.121. PMID: 35858751.
Fabbri L, Chakraborty A, Robert C, Vagner S (2021). The plasticity of mRNA translation during cancer progression and therapy resistance. Nat Rev Cancer. 21(9):558-577. doi: 10.1038/s41568-021-00380-y. PMID: 34341537.
Dutertre M*, Sfaxi R, Vagner S* (2021). Reciprocal Links between Pre-messenger RNA 3'-End Processing and Genome Stability. Trends Biochem Sci. 46(7):579-594. doi: 10.1016/j.tibs.2021.01.009. PMID: 33653631.
Shen S, Vagner S*, Robert C* (2020). Persistent Cancer Cells: The Deadly Survivors. Cell. 183(4):860-874. doi: 10.1016/j.cell.2020.10.027. PMID: 33186528.
Tanaka I, Chakraborty A, Saulnier O, Benoit-Pilven C, Vacher S, Labiod D, Lam EWF, Bièche I, Delattre O, Pouzoulet F, Auboeuf D, Vagner S, Dutertre M. (2020). ZRANB2 and SYF2-mediated splicing programs converging on ECT2 are involved in breast cancer cell resistance to doxorubicin. Nucleic Acids Res. 18;48(5):2676-2693. PMID: 31943118.
Tran Quang C, Zaniboni B, Humeau R, Lengliné E, Dourthe ME, Ganesan R, Singh S, Scheer JM, Asnafi V, Ghysdael J (2020). Preclinical efficacy of humanized, non-FcγR-binding anti-CD3 antibodies in T-cell acute lymphoblastic leukemia. Blood. 136(11):1298-1302. doi: 10.1182/blood.2019003801. PMID: 32483610.
Shen S, Faouzi S, Bastide A, Martineau S, Malka-Mahieu H, Fu Y, Sun X, Mateus C, Routier E, Roy S, Desaubry L, André F, Eggermont A, David A, Scoazec JY, Vagner S*, Robert C* (2019). An epitranscriptomic mechanism underlies selective mRNA translation remodelling in melanoma persister cells. Nat Commun. 10(1):5713. doi: 10.1038/s41467-019-13360-6. PMID: 31844050.
Cerezo M#, Guemiri R#, Druillennec S, Girault I, Malka-Mahieu H, Shen S, Allard D, Martineau S, Welsch C, Agoussi S, Estrada C, Adam J, Libenciuc C, Routier E, Roy S, Désaubry L, Eggermont AM, Sonenberg N, Scoazec JY, Eychène A, Vagner S*, Robert C*. (2018) Translational control of tumor immune escape via the eIF4F-STAT1-PDL1 axis in melanoma. Nat Med. 24(12):1877-1886. PMID: 30374200.
Trinquand A#, Dos Santos NR#, Tran Quang C#, Rocchetti F, Zaniboni, B, Belhocine, M, Da Costa De Jesus C, Lhermitte L, Tesio M, Dussiot M, Cosset F, Verhoeyen E, Pflumio F, Ifrah N, Dombret H, Spicuglia S, Chatenoud L, Gross DA, Hermine O, Macintyre E, Ghysdael J*, Asnafi V* (2016) Triggering The Tcr Developmental Checkpoint Activates A Therapeutically Targetable Tumor Suppressive Pathway In T-Cell Leukemia. Cancer Discov. 6(9):972-85. doi: 10.1158/2159-8290.CD-15-0675. PMID: 27354269.
Passaro D, Irigoyen M, Catherinet C, Gachet S, Da Costa De Jesus C, Lasgi C, Tran Quang C, Ghysdael J (2015). CXCR4 Is Required For Leukemia Initiating Cell Activity In T-Cell Acute Lymphoblastic Leukemia. Cancer Cell. 27(6):769-79. doi: 10.1016/j.ccell.2015.05.003. PMID: 26058076.
Boussemart L, Malka-Mahieu H, Girault I, Allard D, Hemmingsson O, Tomasic G, Thomas M, Basmadjian C, Ribeiro N, Thuaud F, Mateus C, Routier E, Kamsu-Kom N, Agoussi S, Eggermont AM, Desaubry L, Robert C*, Vagner S* (2014) eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies. Nature. 513(7516):105-9. doi: 10.1038/nature13572. PMID: 25079330.
Dutertre M, Lambert S, Carreira A, Amor-Guéret M, Vagner S (2014). DNA damage: RNA-binding proteins protect from near and far. Trends Biochem Sci. 39(3):141-9. doi: 10.1016/j.tibs.2014.01.003. Epub 2014 Feb 14. PMID: 24534650.
Dutertre M$, Chakrama FZ, Combe E, Desmet FO, Mortada H, Polay Espinoza M, Gratadou L, Auboeuf D (2014). A recently evolved class of alternative 3'-terminal exons involved in cell cycle regulation by topoisomerase inhibitors. Nat Commun. 5:3395. doi: 10.1038/ncomms4395. PMID: 24577238 ($corresponding author).
