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13 pages, 2530 KiB

Open AccessCommunication

RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment

by Vladimír Čermák, Aneta Škarková, Ladislav Merta, Veronika Kolomazníková, Veronika Palušová, Stjepan Uldrijan, Daniel Rösel and Jan Brábek

Biomolecules 2021, 11(3), 449; https://doi.org/10.3390/biom11030449 - 17 Mar 2021

Cited by 1 | Viewed by 2769

Abstract

Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, [...] Read more.

Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid–mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis. Full article

(This article belongs to the Special Issue Integrative Analysis of Cancer Cell Signaling Networks by Proteomics and Systems Biology)

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8 pages, 1606 KiB

Open AccessArticle

System-Wide Analysis of Protein Acetylation and Ubiquitination Reveals a Diversified Regulation in Human Cancer Cells

by Hiroko Kozuka-Hata, Aya Kitamura, Tomoko Hiroki, Aiko Aizawa, Kouhei Tsumoto, Jun-ichiro Inoue and Masaaki Oyama

Biomolecules 2020, 10(3), 411; https://doi.org/10.3390/biom10030411 - 06 Mar 2020

Cited by 8 | Viewed by 3312

Abstract

Post-translational modifications are known to be widely involved in the regulation of various biological processes, through the extensive diversification of each protein function at the cellular network level. In order to unveil the system-wide function of the protein lysine modification in cancer cell [...] Read more.

Post-translational modifications are known to be widely involved in the regulation of various biological processes, through the extensive diversification of each protein function at the cellular network level. In order to unveil the system-wide function of the protein lysine modification in cancer cell signaling, we performed global acetylation and ubiquitination proteome analyses of human cancer cells, based on high-resolution nanoflow liquid chromatography–tandem mass spectrometry, in combination with the efficient biochemical enrichment of target modified peptides. Our large-scale proteomic analysis enabled us to identify more than 5000 kinds of ubiquitinated sites and 1600 kinds of acetylated sites, from representative human cancer cell lines, leading to the identification of approximately 900 novel lysine modification sites in total. Very interestingly, 236 lysine residues derived from 141 proteins were found to be modified with both ubiquitination and acetylation. As a consequence of the subsequent motif extraction analyses, glutamic acid (E) was found to be highly enriched at the position (−1) for the lysine acetylation sites, whereas the same amino acid was relatively dispersed along the neighboring residues of the lysine ubiquitination sites. Our pathway analysis also indicated that the protein translational control pathways, such as the eukaryotic initiation factor 2 (EIF2) and the ubiquitin signaling pathways, were highly enriched in both of the acetylation and ubiquitination proteome data at the network level. This report provides the first integrative description of the protein acetylation and ubiquitination-oriented systematic regulation in human cancer cells. Full article

(This article belongs to the Special Issue Integrative Analysis of Cancer Cell Signaling Networks by Proteomics and Systems Biology)

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Review

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44 pages, 3926 KiB

Open AccessReview

Post-Translational Modifications That Drive Prostate Cancer Progression

by Ivana Samaržija

Biomolecules 2021, 11(2), 247; https://doi.org/10.3390/biom11020247 - 09 Feb 2021

Cited by 21 | Viewed by 5376

Abstract

While a protein primary structure is determined by genetic code, its specific functional form is mostly achieved in a dynamic interplay that includes actions of many enzymes involved in post-translational modifications. This versatile repertoire is widely used by cells to direct their response [...] Read more.

While a protein primary structure is determined by genetic code, its specific functional form is mostly achieved in a dynamic interplay that includes actions of many enzymes involved in post-translational modifications. This versatile repertoire is widely used by cells to direct their response to external stimuli, regulate transcription and protein localization and to keep proteostasis. Herein, post-translational modifications with evident potency to drive prostate cancer are explored. A comprehensive list of proteome-wide and single protein post-translational modifications and their involvement in phenotypic outcomes is presented. Specifically, the data on phosphorylation, glycosylation, ubiquitination, SUMOylation, acetylation, and lipidation in prostate cancer and the enzymes involved are collected. This type of knowledge is especially valuable in cases when cancer cells do not differ in the expression or mutational status of a protein, but its differential activity is regulated on the level of post-translational modifications. Since their driving roles in prostate cancer, post-translational modifications are widely studied in attempts to advance prostate cancer treatment. Current strategies that exploit the potential of post-translational modifications in prostate cancer therapy are presented. Full article

(This article belongs to the Special Issue Integrative Analysis of Cancer Cell Signaling Networks by Proteomics and Systems Biology)

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