Targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in metastatic melanoma to increase efficacy of BRAFV600E inhibitors

被引：36

作者：

Kim, TaeWon ^{[1
,2
]}

Havighurst, Thomas ^{[3
]}

Kim, KyungMann ^{[3
,4
]}

Albertini, Mark ^{[4
,5
,6
]}

Xu, Yaohui G. ^{[1
,4
]}

Spiegelman, Vladimir S. ^{[1
,7
]}

机构：

[1] Univ Wisconsin, Dept Dermatol, Sch Med & Publ Hlth, 7th Floor,1 South Pk St, Madison, WI 53715 USA

[2] Univ Wisconsin, Mol & Environm Toxicol Ctr, Sch Med & Publ Hlth, Madison, WI USA

[3] Univ Wisconsin, Dept Biostatist & Med Informat, Sch Med & Publ Hlth, Madison, WI USA

[4] Univ Wisconsin, Carbone Canc Ctr, Sch Med & Publ Hlth, Madison, WI USA

[5] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA

[6] William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI USA

[7] Penn State Univ, Dept Pediat, Hershey, PA USA

来源：

MOLECULAR CARCINOGENESIS | 2018年 / 57卷 / 05期

关键词：

CRD-BP; IGF2BP1; IMP1; resistance to targeted therapies; RNA-binding protein; ACQUIRED-RESISTANCE; BRAF INHIBITOR; CELLS; MUTATIONS; VEMURAFENIB; DABRAFENIB; TRAMETINIB; SURVIVAL; OVERCOME; CANCER;

D O I：

10.1002/mc.22786

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy. Inhibition of IGF2BP1 enhances the effects of BRAF-inhibitor and BRAF-MEK inhibitors in BRAF(V600E) melanoma. Also, knockdown of IGF2BP1 alone is sufficient to reduce tumorigenic characteristics in vemurafenib-resistant melanoma. These findings suggest that IGF2BP1 can be a novel therapeutic target for melanoma.

引用

页码：678 / 683

页数：6

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