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Semaphorins and their Receptors in Stem and Cancer Cells

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Abstract:

There is a growing body of evidence that links cancer with genes and pathways that are required for normal embryonic development, increasing the possibility that cancer cells with stem cell properties, particularly self-renewal and multipotentiality, are primarily involved in tumor formation and progression. One novel pathway that is important in regulating the morphogenesis, proliferation, survival and growth in a variety of adult and embryonic tissues is the semaphorin signaling pathway. Semaphorins are a large family of secreted, transmembrane and GPI-linked proteins with a broad spectrum of functions. Semaphorin signaling is transduced by plexins which, in the case of most class 3 semaphorins, require high affinity neuropilin receptors. The neuropilins also function as receptors for VEGF and other growth factors, and their expression is abnormal in tumors. Various semaphorins can either promote or inhibit tumor progression through the promotion or inhibition of processes such as tumor angiogenesis, metastasis and tumor cell survival. In normal tissues, semaphorin signaling is mainly active in precursor cells. This increases the possibility of tumors being derived from such cells, possibly even stem cells, which are unable to differentiate and/or to stop proliferating. In this review, we summarize the molecular mechanisms of semaphorin signal transduction involved in the stem cell compartment, and describe the evidence that links semaphorins to the control of tumor progression.

Keywords: C-termini; Darwinian model; FAK tyrosine kinases; HGF; Met oncoprotein; Plexin; Proteolytic processing; Receptor tyrosine kinases (RTKs); Receptors; Rho-initiated signaling; Sema3A; Semaphorins; Xenopus spinal neurons; anchorage-independent growth; angiogenesis; anti-CD28; anti-CD3; anti-migratory; anti-migratory effects; autonomously; breast cancer; cancer cells; cancer stem cells; cancerogenesis; cardiovascular system; cell proliferation; chemotaxis; collagen membrane; cysteine residues; dendritic cells (DCs); dorsal root ganglion (DRG); embryogenesis; endodermal cells; endothelial cells; eukaryotes; glioblastoma cell migration; guanosine 3??,5??-monophosphate; hematopoiesis; hepatocyte growth factor (HGF); immune cell migration; intramuscular motoneuron network; intrasubunit disulfide bonds; leukemic cells; lung epithelial cells; marrow-derived cells; mesenchymal; metastasis; misexpression; morphogenesis, proliferation; multiple semaphorin-plexin; neuroendocrine cells; neuropilin (NRP); neuropilin receptors; neuropilins; non-autonomously; olfactory bulb; olfactory sensory axons; organogenesis; plexin cytoplasmic domain; plexin-D1; plexins; plexins type B; pro-migratory; procaryotes; receptor-type kinases; semaphorin proteins; semaphorins; stem cell; stem cells; tumor angiogenesis; tumor metastasis; tumor progression; tumorigenic; vascular endothelial growth factor (VEGF); vasculogenesis; ventricular hypertrophy

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710792927796

Affiliations: Dipartimento di Patologia Molecolare, Politecnica delle Marche, Via Tronto 10/A, 60100, Ancona, Italy.

Publication date: October 1, 2010

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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