Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition

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R-HSA-9926550
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Pathway
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Homo sapiens
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5/5
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Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition
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Studies in melanoma cells have identified MITF-M as a regulator of targets involved in extracellular matrix organization (ECM), focal adhesion (FA) and epithelial-to-mesenchymal transition (EMT) (Dilshat et al, 2021). siRNA-mediated knockdown of MITF-M in the SKMel28 melanoma cell line causes morphological and cytoskeletal changes and promotes formation of aggregates on matrigel, consistent with a role for MITF-M in ECM organization and EMT. CUT-and-RUN analysis identified 101 genes associated with ECM and FA organization that are directly bound by MITF-M and that show increased expression upon siRNA MITF-knockdown (Dilshat et al, 2021), implicating MITF-M as a repressor of these targets in melanoma cells. Of these, 42 were additionally identified as direct MITF-M targets by ChIP-seq in two independent melanoma cell line studies (Laurette et al, 2015; Webster et al, 2014). MITF-M expression levels are correlated with different cellular phenotypes, with high levels corresponding to a more proliferative phenotype and low levels to a quiescent/invasive phenotype, EMT and drug resistance (reviewed in Rambow et al, 2019). Consistent with a role for MITF-M in phenotypic change, EMT-related genes such as CDH1 (E-cadherin), CDH2 (N-cadherin), SOX2 and ZEB1 were also identified as direct MITF-M targets (Dilshat et al, 2021).
Literature References
PubMed ID Title Journal Year
25803486 Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells

Laurette, P, Strub, T, Koludrovic, D, Keime, C, Le Gras, S, Seberg, H, Van Otterloo, E, Imrichova, H, Siddaway, R, Aerts, S, Cornell, RA, Mengus, G, Davidson, I

Elife 2015
33438577 MITF reprograms the extracellular matrix and focal adhesion in melanoma

Dilshat, R, Fock, V, Kenny, C, Gerritsen, I, Lasseur, RMJ, Travnickova, J, Eichhoff, OM, Cerny, P, Möller, K, Sigurbjornsdottir, S, Kirty, K, Einarsdottir, BO, Cheng, PF, Levesque, M, Cornell, RA, Patton, EE, Larue, L, de Tayrac, M, Magnusdottir, E, Ogmundsdottir, MH, Steingrímsson, E

Elife 2021
24443471 Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition

Webster, DE, Barajas, B, Bussat, RT, Yan, KJ, Neela, PH, Flockhart, RJ, Kovalski, J, Zehnder, A, Khavari, PA

Genome Res 2014
31575676 Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities

Rambow, F, Marine, JC, Goding, CR

Genes Dev 2019
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Authored
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Reviewed
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2024-11-01)
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