Alternative Splicing in Adhesion- and Motility-Related Genes in Breast Cancer

• Published in: International journal of molecular sciences Vol. 17; no. 1; p. 121
• Main Authors: Aversa, Rosanna, Sorrentino, Anna, Esposito, Roberta, Ambrosio, Maria Rosaria, Amato, Angela, Zambelli, Alberto, Ciccodicola, Alfredo, D'Apice, Luciana, Costa, Valerio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.01.2016; MDPI
• Subjects: Alternative Splicing; Base Sequence; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Adhesion; Cell adhesion & migration; cell adhesion and motility; Cell Movement; Exons; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Introns; MCF-7 Cells; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Sequencing; Sequence Alignment; Sequence Analysis, DNA; cell adhesion and motility; breast cancer; alternative splicing; RNA-Sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms17010121

Breast cancer is the most common tumor and the second leading cause of cancer death among woman, mainly caused by the metastatic spread. Tumor invasiveness is due to an altered expression of adhesion molecules. Among them, semaphorins are of peculiar interest. Cancer cells can manipulate alternative splicing patterns to modulate the expression of adhesion- and motility-related molecules, also at the isoform level. In this study, combining RNA-Sequencing on MCF-7 to targeted experimental validations-in human breast cell lines and breast tumor biopsies-we identified 12 new alternative splicing transcripts in genes encoding adhesion- and motility-related molecules, including semaphorins, their receptors and co-receptors. Among them, a new SEMA3F transcript is expressed in all breast cell lines and breast cancer biopsies, and is translated into a new semaphorin 3F isoform. In silico analysis predicted that most of the new putative proteins lack functional domains, potentially missing some functions and acquiring new ones. Our findings better describe the extent of alternative splicing in breast cancer and highlight the need to further investigate adhesion- and motility-related molecules to gain insights into breast cancer progression.