共 38 条
Autocrine Signaling of NRP1 Ligand Galectin-1 Elicits Resistance to BRAF-Targeted Therapy in Melanoma Cells
被引:9
作者:

Rizzolio, Sabrina
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机构:
IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy

Corso, Simona
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h-index: 0
机构:
IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy
Univ Torino, Dept Oncol, Med Sch, I-10060 Candiolo, Italy IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy

Giordano, Silvia
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机构:
IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy
Univ Torino, Dept Oncol, Med Sch, I-10060 Candiolo, Italy IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy

Tamagnone, Luca
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h-index: 0
机构:
Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, I-00168 Rome, Italy
IRCCS, Fdn Policlin Univ A Gemelli, I-00168 Rome, Italy IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy
机构:
[1] IRCCS, Candiolo Canc Inst FPO, I-10060 Candiolo, Italy
[2] Univ Torino, Dept Oncol, Med Sch, I-10060 Candiolo, Italy
[3] Univ Cattolica Sacro Cuore, Dept Life Sci & Publ Hlth, I-00168 Rome, Italy
[4] IRCCS, Fdn Policlin Univ A Gemelli, I-00168 Rome, Italy
来源:
关键词:
galectin;
neuropilin;
melanoma;
cancer therapy;
molecular biology;
cell signaling;
oncogenic signaling;
autocrine signaling;
EGFR;
BRAF;
NEUROPILIN-1;
INHIBITOR;
PROLIFERATION;
ACTIVATION;
D O I:
10.3390/cancers12082218
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Melanoma cells addicted to mutated BRAF oncogene activity can be targeted by specific kinase inhibitors until they develop resistance to therapy. We observed that the expression of Galectin-1 (Gal-1), a soluble ligand of Neuropilin-1 (NRP1), is upregulated in melanoma tumor samples and melanoma cells resistant to BRAF-targeted therapy. We then demonstrated that Gal-1 is a novel driver of resistance to BRAF inhibitors in melanoma and that its activity is linked to the concomitant upregulation of the NRP1 receptor observed in drug-resistant cells. Mechanistically, Gal-1 sustains increased expression of NRP1 and EGFR in drug-resistant melanoma cells. Moreover, consistent with its role as a NRP1 ligand, Gal-1 negatively controls p27 levels, a mechanism previously found to enable EGFR upregulation in cancer cells. Finally, the combined treatment with a Gal-1 inhibitor and a NRP1 blocking drug enabled resistant melanoma cell resensitization to BRAF-targeted therapy. In summary, we found that the activation of Galectin-1/NRP1 autocrine signaling is a new mechanism conferring independence from BRAF kinase activity to oncogene-addicted melanoma cells.
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页码:1 / 14
页数:14
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Dana Farber Canc Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

Gu, Chenghua
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Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
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Goel, Hira Lal
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Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA

Mercurio, Arthur M.
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Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA