The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer

Kamiya, Takashi; Kawakami, Tomohiro; Abe, Yoshiyuki; Nishi, Masatake; Onoda, Noboru; Miyazaki, Noriyuki; Oida, Yasuhisa; Yamazaki, Hitoshi; Ueyama, Yoshito; Nakamura, Masato

doi:10.3892/or.15.2.369

Cited by 25 publications

(29 citation statements)

References 20 publications

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“…These effects have been often explained by the role of Nrp1 in supporting VEGF signaling (17,19,20). In contrast to these findings, in other studies, an elevated expression of Nrp1 was associated with more favorable prognosis of patients with colon cancer (21) and reduced tumor growth in experimental models in mice (22); moreover, a VEGF/Nrp1-dependent pathway suppressing cell viability has been proposed in 1 specific case (23). These discrepancies are currently unresolved and they might reflect cell-specific responses and/or the involvement of different signaling pathways.…”

Section: Introductioncontrasting

confidence: 50%

Neuropilin-1–Dependent Regulation of EGF-Receptor Signaling

et al. 2012

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Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 is widely expressed in cancer cells and in advanced human tumors; however, its functional relevance and signaling mechanisms are unclear. Here, we show that NRP1 expression controls viability and proliferation of different cancer cells, independent of its short intracellular tail. We found that the extracellular domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling cascade elicited upon EGF or TGF-a stimulation. Upon NRP1 silencing, the ability of ligand-bound EGFR to cluster on the cell surface, internalize, and activate the downstream AKT pathway is severely impaired. EGFR is frequently activated in human tumors due to overexpression, mutation, or sustained autocrine/paracrine stimulation. Here we show that NRP1-blocking antibodies and NRP1 silencing can counteract ligand-induced EGFR activation in cancer cells. Thus our findings unveil a novel molecular mechanism by which NRP1 can control EGFR signaling and tumor growth. Cancer Res; 72(22); 5801-11. Ó2012 AACR.

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Section: Introductioncontrasting

confidence: 50%

Neuropilin-1–Dependent Regulation of EGF-Receptor Signaling

et al. 2012

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“…Increased expression of Np-1 and Np-2 correlates with tumor aggressiveness, advanced disease stage, and poor prognosis (39–41). In contrast, several studies have reported that Np-1 overexpression in tumor cells reduces motility and tumorigenicity or prolonged patient survival (42–45). Possible reasons for discrepancies between various studies may include the expression of functional receptor/ligand repertoire (e.g., plexins) and/or the ratio of VEGF-A to SEMA3 within the particular tumor microenvironment.…”

Section: Discussionmentioning

confidence: 93%

Semaphorin 3B Inhibits the Phosphatidylinositol 3-Kinase/Akt Pathway through Neuropilin-1 in Lung and Breast Cancer Cells

Castro-Rivera¹,

Ran

Brekken

et al. 2008

Cancer Research

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Semaphorin 3B (SEMA3B), located at 3p21.3, is a secreted member of the semaphorin family important in axonal guidance. SEMA3B undergoes allele and expression loss in lung and breast cancer and can function as a tumor suppressor. Previously, we found that SEMA3B induces apoptosis in tumor cells either by reexpression or when applied as a soluble ligand. SEMA3B-induced apoptosis was mediated, in part, by blocking vascular endothelial growth factor autocrine activity in tumor cells. In the current study, treatment of lung and breast cancer cells with picomolar concentrations of soluble SEMA3B inhibited their growth; induced apoptosis; and was associated with decreased Akt phosphorylation, increase in cytochrome c release and caspase-3 cleavage, as well as increased phosphorylation of several proapoptotic proteins, including glycogen synthase kinase-3B, FKHR, and MDM-2. Lung and breast cancer lines resistant to SEMA3B did not show these signaling changes and a tumor-derived missense SEMA3B mutant was inactive in this regard, providing specificity. SEMA3B-mediated inhibition of proliferation and induction of apoptosis in cancer cells were blocked by expressing a constitutively active Akt mutant and are linked to tumor cell expression of neuropilin-1 (Np-1). SEMA3B-insensitive Np-1-negative tumor cells acquired sensitivity to SEMA3B after forced expression of Np-1, whereas SEMA3B-sensitive Np-1-positive tumor cells lost sensitivity to SEMA3B after knockdown of Np-1 by small interfering RNA. We conclude that SEMA3B is a potential tumor suppressor that induces apoptosis in SEMA3B-inactivated tumor cells through the Np-1 receptor by inactivating the Akt signaling pathway. [Cancer Res 2008;68(20):8295-303]

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“…5,[15][16][17] Although the prognostic impact of NRP-1 expression in AML was unknown so far, the prognostic value of NRP-1 expression in solid tumors has already been investigated by others. Preserved expression of NRP-1 contributes to a better prognosis in colon cancer, 18 whereas overexpression of NRP-1 correlates with poor prognosis in human glioma. 19 In non-smallcell lung cancer (NSCLC), co-expression of NRP-1 and NRP-2 is associated with poorer prognosis.…”

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confidence: 99%

Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia

et al. 2006

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Neuropilin-1 (NRP-1), a vascular endothelial growth factors and semaphorin receptor functioning as mediator of angiogenesis and neuronal guidance, is expressed by various solid tumors. The importance of NRP-1 in hematological malignancies such as acute myeloid leukemia (AML) remains to be elucidated. Therefore, we determined NRP-1 expression by immunohistochemical analysis of bone marrow biopsies of patients with newly diagnosed, untreated AML. The expression of NRP-1 was significantly increased in AML patients (n ¼ 76; median 12.9 arbitrary units (a.u.)) as compared with controls (n ¼ 38; median 2.75 a.u.). Survival was significantly poorer in patients with high (4median) versus low (pmedian) NRP-1 expression levels with 5-year overall survival rates of 16.9 versus 49.6% (P ¼ 0.050). In conclusion, our data provide evidence of increased NRP-1 expression in AML with significant correlation to survival. Thus, NRP-1 might constitute a promising target for antileukemic and antiangiogenic treatment strategies in AML.

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The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer

Cited by 25 publications

References 20 publications

Neuropilin-1–Dependent Regulation of EGF-Receptor Signaling

Neuropilin-1–Dependent Regulation of EGF-Receptor Signaling

Semaphorin 3B Inhibits the Phosphatidylinositol 3-Kinase/Akt Pathway through Neuropilin-1 in Lung and Breast Cancer Cells

Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia

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