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VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells.

Yoshida A, Shimizu A, Asano H, Kadonosono T, Kondoh SK, Geretti E, Mammoto A, Klagsbrun M, Seo MK - Biol Open (2015)

Bottom Line: DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1.Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor.In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

View Article: PubMed Central - PubMed

Affiliation: Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kyoto 603-8555, Japan.

No MeSH data available.


Related in: MedlinePlus

Schematic of the VEGF-A/NRP1 signaling pathway to promote cancer cell proliferation. Schematic of a new pathway of NRP1 signals leading to the proliferation of cancer cells. Cancer cell-secreted VEGF-A binds to NRP1 in an autocrine manner and stimulates complex formation by GIPC1, a scaffold protein, and Syx, RhoGEF, via the NRP1 cytoplasmic region. The GIPC1/Syx complex increases the activation of RhoA in order to induce the degradation of p27 and consequently promotes cancer cell proliferation.
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BIO010918F8: Schematic of the VEGF-A/NRP1 signaling pathway to promote cancer cell proliferation. Schematic of a new pathway of NRP1 signals leading to the proliferation of cancer cells. Cancer cell-secreted VEGF-A binds to NRP1 in an autocrine manner and stimulates complex formation by GIPC1, a scaffold protein, and Syx, RhoGEF, via the NRP1 cytoplasmic region. The GIPC1/Syx complex increases the activation of RhoA in order to induce the degradation of p27 and consequently promotes cancer cell proliferation.

Mentions: In the present study, VEGF-A induced the cancer cell proliferation of PC3M (prostate cancer), DJM-1 (skin cancer), and U87MG (glioblastoma cell) in an anchorage-independent manner via the NRP1 signaling pathway (Fig. 8). The knockdown of VEGF-A or NRP1 abrogated the proliferation of these cancer cells. We selected skin cancer-derived DJM-1 cells, which only express NRP1 as the VEGF-A receptor and grow faster than other cancer cells under anchorage-independent conditions.Fig. 8.


VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells.

Yoshida A, Shimizu A, Asano H, Kadonosono T, Kondoh SK, Geretti E, Mammoto A, Klagsbrun M, Seo MK - Biol Open (2015)

Schematic of the VEGF-A/NRP1 signaling pathway to promote cancer cell proliferation. Schematic of a new pathway of NRP1 signals leading to the proliferation of cancer cells. Cancer cell-secreted VEGF-A binds to NRP1 in an autocrine manner and stimulates complex formation by GIPC1, a scaffold protein, and Syx, RhoGEF, via the NRP1 cytoplasmic region. The GIPC1/Syx complex increases the activation of RhoA in order to induce the degradation of p27 and consequently promotes cancer cell proliferation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582117&req=5

BIO010918F8: Schematic of the VEGF-A/NRP1 signaling pathway to promote cancer cell proliferation. Schematic of a new pathway of NRP1 signals leading to the proliferation of cancer cells. Cancer cell-secreted VEGF-A binds to NRP1 in an autocrine manner and stimulates complex formation by GIPC1, a scaffold protein, and Syx, RhoGEF, via the NRP1 cytoplasmic region. The GIPC1/Syx complex increases the activation of RhoA in order to induce the degradation of p27 and consequently promotes cancer cell proliferation.
Mentions: In the present study, VEGF-A induced the cancer cell proliferation of PC3M (prostate cancer), DJM-1 (skin cancer), and U87MG (glioblastoma cell) in an anchorage-independent manner via the NRP1 signaling pathway (Fig. 8). The knockdown of VEGF-A or NRP1 abrogated the proliferation of these cancer cells. We selected skin cancer-derived DJM-1 cells, which only express NRP1 as the VEGF-A receptor and grow faster than other cancer cells under anchorage-independent conditions.Fig. 8.

Bottom Line: DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1.Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor.In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

View Article: PubMed Central - PubMed

Affiliation: Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kyoto 603-8555, Japan.

No MeSH data available.


Related in: MedlinePlus