Semaphorins and their Receptors in Stem and Cancer Cells

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 semaphoring 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, semaphoring 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.

Proteomic Analyses of Lung Lysates from Short-Term Exposure of Fischer 344 Rats to Cigarette Smoke

“…CRMP2 binds to tubulin and promotes microtubulin assembly. Class 3 semaphorins are secreted proteins that alter the cytoskeleton and organization of actin filaments and microtubules and play a role in tumor formation or prevention …”

“…Class 3 semaphorins are secreted proteins that alter the cytoskeleton and organization of actin filaments and microtubules and play a role in tumor formation or prevention. 40 Cigarette smoke increases ERK1/2 phosphorylation in airway lining cells and alveolar macrophages in mice exposed for 10 days and 6 months. 41 ERK1/2 also significantly increases in lung tissues from emphysema patients compared to controls.…”

Plexin-B3 Regulates Cellular Motility, Invasiveness, and Metastasis in Pancreatic Cancer

“…Many recent reports have revealed that axon guidance cue molecules like the semaphorin /plexin axis are hijacked by different cancer cells to aid in their growth, differentiation, and renewal of cancer stem-like cells [31][32][33][34]. Our interest in investigating the role of Plexin-B3 in stem cell properties of PC cells came from various studies that demonstrate Plexin-B's role in regulating the stemness of different cancers [30,[35][36][37].…”

Plexin-B1: A potential diagnostic biomarker for glioma and a future target for glioma immunotherapy

“…Another study demonstrated the requirement for CD100 in the induction of antigen-specific T cells and the maturation of DCs (Kumanogoh et al, 2002). Recent study showed that semaphorins and their receptors were primarily involved in tumor formation and progression (Micucci et al, 2010). However, the expression of Plexin-B1 by gliomas and its relationship with the pathological progression of this tumor type remain unclear.…”