E2F1 Inhibition Mediates Cell Death of Metastatic Melanoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 May 11

PMID 29743521

Citations 23

Authors

Florian Rouaud

Nedra Hamouda-Tekaya

Michael Cerezo

Patricia Abbe

Josephine Zangari

Veronique Hofman

Mickael Ohanna

Baharia Mograbi

Najla El-Hachem

Zohra Benfodda

Alexandre Lebeau

Meri K Tulic

Paul Hofman

Corine Bertolotto

Thierry Passeron

Jean-Sebastien Annicotte

Robert Ballotti

Stephane Rocchi

Affiliations

Soon will be listed here.

Abstract

Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and achieve more prolonged responses. In this context, we were interested in E2F1, a transcription factor that plays a major role in the control of cell cycle under physiological and pathological conditions. Here we confirmed that E2F1 is highly expressed in melanoma cells. Inhibition of E2F1 activity further increased melanoma cell death and senescence, both in vitro and in vivo. Moreover, blocking E2F1 also induced death of melanoma cells resistant to BRAF inhibitors. In conclusion, our studies suggest that targeting the E2F1 signaling pathway may be therapeutically relevant for melanoma.

Citing Articles

Novel liquid biopsy CNV biomarkers in malignant melanoma.

Lukacova E, Hanzlikova Z, Podlesnyi P, Sedlackova T, Szemes T, Grendar M Sci Rep. 2024; 14(1):15786.

PMID: 38982214 PMC: 11233564. DOI: 10.1038/s41598-024-65928-y.

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

Cameron C, Richardson B, Golden J, Phoon Y, Tamilselvan B, Pfannenstiel L Front Oncol. 2023; 13:1200387.

PMID: 38023136 PMC: 10643547. DOI: 10.3389/fonc.2023.1200387.

Logic-based modeling and drug repurposing for the prediction of novel therapeutic targets and combination regimens against E2F1-driven melanoma progression.

Singh N, Khan F, Bala L, Vera J, Wolkenhauer O, Putzer B BMC Chem. 2023; 17(1):161.

PMID: 37993971 PMC: 10666365. DOI: 10.1186/s13065-023-01082-2.

Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling.

Howell R, Davies J, Clarke M, Appios A, Mesquita I, Jayal Y Sci Adv. 2023; 9(15):eadd1992.

PMID: 37043573 PMC: 10096595. DOI: 10.1126/sciadv.add1992.

as a potential prognostic and therapeutic biomarker by affecting tumor development and immune microenvironment in hepatocellular carcinoma.

Tan Z, Chen M, Peng F, Yang P, Peng Z, Zhang Z Transl Cancer Res. 2022; 11(8):2713-2732.

PMID: 36093522 PMC: 9459514. DOI: 10.21037/tcr-22-218.

References

Ott P, Hodi F, Robert C . CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable clinical benefit in melanoma patients. Clin Cancer Res. 2013; 19(19):5300-9. DOI: 10.1158/1078-0432.CCR-13-0143. View

Sosman J, Kim K, Schuchter L, Gonzalez R, Pavlick A, Weber J . Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012; 366(8):707-14. PMC: 3724515. DOI: 10.1056/NEJMoa1112302. View

Millet A, Martin A, Ronco C, Rocchi S, Benhida R . Metastatic Melanoma: Insights Into the Evolution of the Treatments and Future Challenges. Med Res Rev. 2016; 37(1):98-148. DOI: 10.1002/med.21404. View

Phalke S, Mzoughi S, Bezzi M, Jennifer N, Mok W, Low D . p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6. Nucleic Acids Res. 2012; 40(19):9534-42. PMC: 3479215. DOI: 10.1093/nar/gks858. View

Rouaud F, Boucher J, Slama-Schwok A, Rocchi S . Mechanism of melanoma cells selective apoptosis induced by a photoactive NADPH analogue. Oncotarget. 2016; 7(50):82804-82819. PMC: 5347734. DOI: 10.18632/oncotarget.12651. View

Ma Y, Kurtyka C, Boyapalle S, Sung S, Lawrence H, Guida W . A small-molecule E2F inhibitor blocks growth in a melanoma culture model. Cancer Res. 2008; 68(15):6292-9. PMC: 3615411. DOI: 10.1158/0008-5472.CAN-08-0121. View

Lehraiki A, Abbe P, Cerezo M, Rouaud F, Regazzetti C, Chignon-Sicard B . Inhibition of melanogenesis by the antidiabetic metformin. J Invest Dermatol. 2014; 134(10):2589-2597. DOI: 10.1038/jid.2014.202. View

Meng P, Ghosh R . Transcription addiction: can we garner the Yin and Yang functions of E2F1 for cancer therapy?. Cell Death Dis. 2014; 5:e1360. PMC: 4454301. DOI: 10.1038/cddis.2014.326. View

Giuliano S, Cheli Y, Ohanna M, Bonet C, Beuret L, Bille K . Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas. Cancer Res. 2010; 70(9):3813-22. DOI: 10.1158/0008-5472.CAN-09-2913. View

10.

Flaherty K, Puzanov I, Kim K, Ribas A, McArthur G, Sosman J . Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010; 363(9):809-19. PMC: 3724529. DOI: 10.1056/NEJMoa1002011. View

11.

Botton T, Puissant A, Cheli Y, Tomic T, Giuliano S, Fajas L . Ciglitazone negatively regulates CXCL1 signaling through MITF to suppress melanoma growth. Cell Death Differ. 2010; 18(1):109-21. PMC: 3131866. DOI: 10.1038/cdd.2010.75. View

12.

Talantov D, Mazumder A, Yu J, Briggs T, Jiang Y, Backus J . Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res. 2005; 11(20):7234-42. DOI: 10.1158/1078-0432.CCR-05-0683. View

13.

Das Thakur M, Salangsang F, Landman A, Sellers W, Pryer N, Levesque M . Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013; 494(7436):251-5. PMC: 3930354. DOI: 10.1038/nature11814. View

14.

Nelson M, Reynolds S, Rao U, Goulet A, Feng Y, Beas A . Increased gene copy number of the transcription factor E2F1 in malignant melanoma. Cancer Biol Ther. 2006; 5(4):407-12. DOI: 10.4161/cbt.5.4.2512. View

15.

Engelmann D, Putzer B . The dark side of E2F1: in transit beyond apoptosis. Cancer Res. 2012; 72(3):571-5. DOI: 10.1158/0008-5472.CAN-11-2575. View

16.

Blanchet E, Annicotte J, Fajas L . Cell cycle regulators in the control of metabolism. Cell Cycle. 2009; 8(24):4029-31. PMC: 3323501. DOI: 10.4161/cc.8.24.10110. View

17.

Cerezo M, Tichet M, Abbe P, Ohanna M, Lehraiki A, Rouaud F . Metformin blocks melanoma invasion and metastasis development in AMPK/p53-dependent manner. Mol Cancer Ther. 2013; 12(8):1605-15. DOI: 10.1158/1535-7163.MCT-12-1226-T. View

18.

Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M, Pagano M . An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. Mol Cell. 2004; 16(1):47-58. DOI: 10.1016/j.molcel.2004.09.029. View

19.

Passos J, Nelson G, Wang C, Richter T, Simillion C, Proctor C . Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010; 6:347. PMC: 2835567. DOI: 10.1038/msb.2010.5. View

20.

Corazao-Rozas P, Guerreschi P, Jendoubi M, Andre F, Jonneaux A, Scalbert C . Mitochondrial oxidative stress is the Achille's heel of melanoma cells resistant to Braf-mutant inhibitor. Oncotarget. 2013; 4(11):1986-98. PMC: 3875764. DOI: 10.18632/oncotarget.1420. View