Results of transductions were identical for all lambda phages

re research. Mutations and copy number variations in splicing regulators have been identified in several types of cancer, supporting the notion that changes in splicing fidelity contribute to cancer development. Alternative splicing plays a major role in cancer development and progression as many tumor suppressors and oncogenes are modulated by alternative splicing. However, the role of alternative splicing regulators in cancer development is mostly unknown, and only recently the first direct evidence for an oncogenic role of a splicing factor has been shown. The Ras-MAPK and PI3K-mTOR signalling pathways are deregulated in many cancers by genetic and epigenetic aberrations. Several key components in these pathways, such as Ras, B-RAF, C-RAF, MEK1, PI3K, and Akt, are activated by mutations or gene amplifications, while other components that inhibit these pathways, such as PTEN, LKB1, and TSC1/2, are inactivated by genomic deletions and mutations. Pharmacological inhibitors of enzymes in these pathways, such as BRAF inhibitors and mTOR inhibitors, are already being used in clinical settings PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19819508 to treat cancer, while others are in advanced stages of clinical trials. Although the Ras-MAPK and PI3K-mTOR pathways are at the center of intensive research, and many genetic alterations that activate or inactivate these pathways have been discovered, much less is known about the epigenetic and posttranscriptional regulation of these signalling pathways. Recent studies have revealed how these pathways can be regulated by alternative splicing and by splicing regulators and are the focus of this review. Here, we discuss the intricate relationship between alternative splicing and signalling at different levels: how the 2 International Journal of Cell Biology Signalling component RTK Gene name EGFR Splicing isoform activity Constitutively active receptor/soluble decoy isoform, enhanced signalling, survival, and tumorigenicity. Constitutively active receptor, enhanced signalling, invasion, and motility. Constitutively active receptor/soluble decoy isoform, enhanced/reduced signalling, invasion, and motility. Induction of EMT, invasion, and motility. Differential ligand binding and oncogenic activity. Soluble decoy isoform, enhanced/reduced angiogenesis, and survival. Enhanced/reduced kinase activity, survival of epithelial cells. Constitutively active kinase, oncogenic activity. Tumor suppressor/oncogenic isoforms, activates/inhibits mTORC1. Enhanced/reduced binding to Ras and activation of the MAPK pathway. Enhanced/reduced kinase activity, activation of the MAPK pathway, and resistance to BRAF kinase inhibitors. Alternative pathway with a different substrate. Alternative pathway with different substrates. Oncogenic isoform that enhances eIF4E phosphorylation and a tumor-suppressive isoform. Active/inactive tumor suppressor. Constitutively active kinase, enhanced downstream signalling. Enhanced/reduced binding to Raf and Rin and activation of the MAPK pathway. Inactivation of a tumor suppressor. Type of cancer Glioblastoma, lung Glioblastoma, colon, breast, and gastric Ovarian, lung, and HCC Prostate, pancreatic, and Varlitinib site breast HCC, thyroid, and ovarian Lung, breast Unknown HCC Breast, lung HCC, head, and neck Colon, melanoma Unknown Unknown Lung, breast, colon, and pancreas Unknown Unknown Unknown Tuberous sclerosis Diverse derivatives of platinum are used as therapeutic agents in cancer treatment. Among them, cisplatin, cis-diaminodichloroplatinum, a neutr