The cytoskeleton of animal cells is one of the most complicated and functionally versatile structures, involved in processes such as endocytosis, cell division, intra-cellular transport, motility, force transmission, reaction to external forces, adhesion and preservation, and adaptation of cell shape. These functions are mediated by three classical cytoskeletal filament types, as follows: Actin, microtubules, and intermediate filaments. The named filaments form a network that is highly structured and dynamic, responding to external and internal cues with a quick reorganization that is orchestrated on the time scale of minutes and has to be tightly regulated. Especially in brain tumors, the cytoskeleton plays an important role in spreading and migration of tumor cells. As the cytoskeletal organization and regulation is complex and many-faceted, this review aims to summarize the findings about cytoskeletal filament types, including substructures formed by them, such as lamellipodia, stress fibers, and interactions between intermediate filaments, microtubules and actin. Additionally, crucial regulatory aspects of the cytoskeletal filaments and the formed substructures are discussed and integrated into the concepts of cell motility. Even though little is known about the impact of cytoskeletal alterations on the progress of glioma, a final point discussed will be the impact of established cytoskeletal alterations in the cellular behavior and invasion of glioma.

https://www.mdpi.com/2073-4409/8/4/362/pdf

The Cytoskeleton-A Complex Interacting Meshwork.

Activation of the Raf/MAP kinase pathway is a critical event in tumorigenesis induced by RAS and other oncogenes, a major role of this signaling system being the regulation of cellular transcription factors. To address the contribution of MAP kinase mediated transcriptional changes to the transformed phenotype, we used an inducible form of Raf to analyze early changes in the transcription of some 6000 genes following activation of the kinase in a normal human breast epithelial cell line. Of the more than 120 significant changes in mRNA level detected, genes promoting cell proliferation, invasiveness, and angiogenesis featured prominently. Some of the most strongly induced genes encoded growth factors of the EGF family: Autocrine activation of the EGF receptor was shown to be responsible for the ability of Raf activation to protect these cells from apoptosis induced by detachment of cells from extracellular matrix (anoikis), which is a critical component of the transformed phenotype.

/pdf/analysis-of-the-transcriptional-program-induced-by-raf-in-1u73sbiuts.pdf

Analysis of the transcriptional program induced by Raf in epithelial cells

BRAF and KRAS are two key oncogenes in the RAS/RAF/MEK/MAPK signaling pathway. Concomitant mutations in both KRAS and BRAF genes have been identified in non-small cell lung cancer (NSCLC). They lead to the proliferation, differentiation, and apoptosis of tumor cells by activating the RAS/RAF/MEK/ERK signaling pathway. To date, agents that target RAS/RAF/MEK/ERK signaling pathway have been investigated in NSCLC patients harboring BRAF mutations. BRAF and MEK inhibitors have gained approval for the treatment of patients with NSCLC. According to the reported findings, the combination of MEK inhibitors with chemotherapy, immune checkpoint inhibitors, epidermal growth factor receptor-tyrosine kinase inhibitors or BRAF inhibitors is highly significant for improving clinical efficacy and causing delay in the occurrence of drug resistance. This review summarized the existing experimental results and presented ongoing clinical studies as well. However, further researches need to be conducted to indicate how we can combine other drugs with MEK inhibitors to significantly increase therapeutic effects on patients with lung cancer.

/pdf/mek-inhibitors-for-the-treatment-of-non-small-cell-lung-1m8pgopmye.pdf

MEK inhibitors for the treatment of non-small cell lung cancer

The attachment of cells to the extracellular matrix (ECM) is the hallmark of structure-function stability and well-being ECM detachment in localized tumors precedes abnormal dissemination of tumor cells culminating in metastasis Programmed cell death (PCD) is activated during tumorigenesis to clear off ECM-detached cells through "anoikis" However, cancer cells develop several mechanisms for abrogating anoikis, thus promoting their invasiveness and metastasis Specific factors, such as growth proteins, pH, transcriptional signaling pathways, and oxidative stress, have been reported as drivers of anoikis resistance, thus enhancing cancer proliferation and metastasis Recent studies highlighted the key contributions of metabolic pathways, enabling the cells to bypass anoikis Therefore, understanding the mechanisms driving anoikis resistance could help to counteract tumor progression and prevent metastasis This review elucidates the dynamics employed by cancer cells to impede anoikis, thus promoting proliferation, invasion, and metastasis In addition, the authors have discussed other metabolic intermediates (especially amino acids and nucleotides) that are less explored, which could be crucial for anoikis resistance and metastasis

/pdf/mechanisms-for-modulating-anoikis-resistance-in-cancer-and-2j30f0dmmm.pdf

Mechanisms for Modulating Anoikis Resistance in Cancer and the Relevance of Metabolic Reprogramming.

As an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.

/pdf/advances-in-rna-cytosine-5-methylation-detection-regulatory-yg1pnbo5yn.pdf

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer.

Mitogen-activated protein kinase (MAPK) cascades are key signalling pathways that regulate a wide variety of cellular processes, including proliferation, differentiation, apoptosis and stress responses. The MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, which activate and phosphorylate downstream proteins. The extracellular signal-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that regulate cellular signalling under both normal and pathological conditions. ERK expression is critical for development and their hyperactivation plays a major role in cancer development and progression. The Ras/Raf/MAPK (MEK)/ERK pathway is the most important signalling cascade among all MAPK signal transduction pathways, and plays a crucial role in the survival and development of tumour cells. The present review discusses recent studies on Ras and ERK pathway members. With respect to processes downstream of ERK activation, the role of ERK in tumour proliferation, invasion and metastasis is highlighted, and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.

/pdf/erk-mapk-signalling-pathway-and-tumorigenesis-23yie24hev.pdf

ERK/MAPK signalling pathway and tumorigenesis.

The promyelocytic leukemia (PML) gene is a tumor suppressor gene It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation The function of the PML protein is frequently lost or aberrant in human solid tumors In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence Proliferation and clone number of PML-depleted cells were detected using MTT assay and colony-forming assay The protein expression associated with DNA damage and apoptosis was assessed in PML-depleted cells using western blot analysis and immunofluorescence The results showed that PML was highly expressed in human ovarian tissue The proliferation and colony formation of ovarian cancer cells were significantly inhibited after PML was depleted Western blot analysis and immunofluorescence revealed that p-H2AX and cleaved caspase-3 expression significantly increased after PML silencing PML was located in the nucleus, and it formed foci after X-ray irradiation PML foci increased significantly with increasing irradiation doses

/pdf/pml-silencing-inhibits-cell-proliferation-and-induces-dna-13g2ebt82l.pdf

Ying Xu

Papers

ERK/MAPK signalling pathway and tumorigenesis.

PML silencing inhibits cell proliferation and induces DNA damage in cultured ovarian cancer cells