The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells

被引：31

作者：

Zalfa, Francesca ^{[1
]}

Panasiti, Vincenzo ^{[1
]}

Carotti, Simone ^{[1
]}

Zingariello, Maria ^{[1
]}

Perrone, Giuseppe ^{[1
]}

Sancillo, Laura ^{[2
]}

Pacini, Laura ^{[3
]}

Luciani, Flavie ^{[4
,5
]}

Roberti, Vincenzo ^{[6
]}

D'Amico, Silvia ^{[3
]}

Coppola, Rosa ^{[1
]}

Abate, Simona Osella ^{[7
]}

Rana, Rosa Alba ^{[2
]}

De Luca, Anastasia ^{[3
]}

Fiers, Mark ^{[4
,5
]}

Melocchi, Valentina ^{[8
]}

Bianchi, Fabrizio ^{[8
]}

Farace, Maria Giulia ^{[3
]}

Achsel, Tilmann ^{[4
,5
]}

Marine, Jean-Christophe ^{[4
,5
]}

Morini, Sergio ^{[1
]}

Bagni, Claudia ^{[3
,4
,5
,9
]}

机构：

[1] Campus Biomed Univ, Dept Med, Via Alvaro del Portillo 21, I-00128 Rome, Italy

[2] Univ G dAnnunzio, Dept Med & Sci Aging, Via Vestini 31, I-66100 Chieti, Italy

[3] Univ Roma Tor Vergata, Dept Biomed & Prevent, Via Montpellier 1, I-00133 Rome, Italy

[4] Katholieke Univ Leuven, VIB Ctr Biol Dis, O&N 4,Herestr 49 Box 602, B-3000 Leuven, Belgium

[5] Katholieke Univ Leuven, Ctr Human Genet, Leuven Inst Neurosci & Dis, O&N 4,Herestr 49 Box 602, B-3000 Leuven, Belgium

[6] Univ Roma La Sapienza, Dept Dermatol, Viale Univ 1, I-00185 Rome, Italy

[7] Univ Turin, Sect Dermatooncol, Dept Med Sci & Human Oncol, Via Verdi 8, I-10124 Turin, Italy

[8] IRCCS Casa Sollievo Sofferenza, Inst Stem Cell Biol Regenerat Med & Innovat Thera, ISBREMIT, Viale Padre Pio 7, I-71013 San Giovanni Rotondo, FG, Italy

[9] Univ Lausanne, Dept Fundamental Neurosci, Rue Bugnon 9, CH-1005 Lausanne, Switzerland

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

关键词：

MESSENGER-RNA TRANSPORT; HEPATOCELLULAR-CARCINOMA; DEPENDENT TRANSLATION; GENE-EXPRESSION; MYOSIN VA; CANCER; FMRP; KINESIN; TARGETS; IDENTIFICATION;

D O I：

10.1038/cddis.2017.521

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level. Furthermore, metaanalysis of the TCGA melanoma data revealed that high levels of FMRP expression correlate significantly with metastatic tumor tissues, risk of relapsing and disease-free survival. Reduction of FMRP in metastatic melanoma cell lines impinges on cell migration, invasion and adhesion. Next-generation sequencing in human melanoma cells revealed that FMRP regulates a large number of mRNAs involved in relevant processes of melanoma progression. Our findings suggest an association between FMRP levels and the invasive phenotype in melanoma and might open new avenues towards the discovery of novel therapeutic targets.

引用

页码：e3169 / e3169

页数：12

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