Biology and pathology of melanocyte cells : From skin pigmentation to melanomas

Previous activities

Our work was focused on the study of the molecular mechanisms involved in melanocyte differentiation. The results we obtained were a major breakthrough in the understanding of the transcription mechanisms and the early signaling events that control the synthesis of melanin pigments and dendricity – both key parameters of melanocyte differentiation. We have shown the major role played by MITF transcription factor in such processes.

We also studied melanosome transport, melanosomes being melanocyte-specific intracellular vesicles where melanin synthesis occurs. Melanosomes are transported to melanocyte’ dendrites tips then transferred to neighboring keratinocytes, which results in an effective protection of melanin against carcinogenic UV rays. We have shown that the small G protein, Rab27a, plays a key role in melanosome transport.

More recently, we have developed new approaches focusing on the study of apoptosis and the microenvironment in which a melanoma develops.

We have highlighted the key role of PI3-kinase pathway in SCF antiapoptotic effects and in melanoma resistance to chemotherapy drugs. Moreover, we have identified MITF as a new caspase substrate during apoptosis of melanocytes and melanomas. Finally, we have shown that MITF regulates at the transcription level the expression of HIF1α?, a transcription factor that plays a key role in neovascularization processes.

We have been the first to describe the signaling pathways involved in the expression of fibronectin in melanomas. This pathway involves the activation of B-Raf and MAP kinases/ ERKs and triggers transcription factor Egr-1.

Moreover, we have shown that the matrix protein SPARC, which expression increases during melanocyte tumour development regulates the early stages of melanocyte transformation by repressing E-cadherine and triggering a mesenchyme-type transition that is that hallmark of an invasive potential. These original findings suggest that SPARC plays a key role in melanocyte transformation.

Research Projects

I. Role of MITF in melanoma survival and development
II. Role of FoxO proteins in melanoma survival and development
III. Role of SPARC in melanoma development .
IV. Role of Syk (Spleen tyrosine kinase) in melanoma development
V- Role of MITF and HIF1A in melanoma development
VI- Analysis of molecular events triggered by UV rays in melanocytes.
VII- Role of PPARγ in melanocytes and melanomas and its involvement in tumor development.
Through their different yet complementary approaches, the projects developed under this program will contribute to the elucidation of the molecular processes controlling melanocyte differentiation, survival and transformation. The results will allow to better unserstand the mechanisms involved in melanin photoprotection, photocancerogenesis and the pathogenesis of skin pigmentation disorders.

Last Publications

Bourseguin J, Bonet C, Renaud E, Pandiani C, Boncompagni M, Giuliano S, Pawlikowska P, Karmous-Benailly H, Ballotti R, Rosselli F, Bertolotto C. FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells. Sci Rep. 2016 Nov 9;6:36539.

Cerezo M, Rocchi S. New anti-cancer molecules targeting HSPA5/BIP to induce Endoplasmic Reticulum stress, autophagy and apoptosis. Autophagy. 2016 Oct 28:0.

Rouaud F, Boucher JL, Slama-Schwok A, Rocchi S. Mechanism of melanoma cells selective apoptosis induced by a photoactive NADPH analogue. Oncotarget. 2016 Oct 14.

Richard G, Dalle S, Monet MA, Ligier M, Boespflug A, Pommier RM, de la Fouchardière A, Perier-Muzet M, Depaepe L, Barnault R, Tondeur G, Ansieau S, Thomas E, Bertolotto C, Ballotti R, Mourah S, Battistella M, Lebbé C, Thomas L, Puisieux A, Caramel J. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors. EMBO Mol Med. 2016 Oct 4;8(10):1143-1161.

Millet A, Plaisant M, Ronco C, Cerezo M, Abbe P, Jaune E, Cavazza E, Rocchi S, Benhida R. Discovery and Optimization of N-(4-(3-Aminophenyl)thiazol-2-yl)acetamide as a Novel Scaffold Active against Sensitive and Resistant Cancer Cells. J Med Chem. 2016 Sep 22;59(18):8276-92.

Millet A, Martin AR, Ronco C, Rocchi S, Benhida R. Metastatic Melanoma: Insights Into the Evolution of the Treatments and Future Challenges. Med Res Rev. 2016 Aug 29.

Team Publications