ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability

Shenghao Wang; Li Tang; Junyu Lin; Zhongliang Shen; Yikun Yao; Wei Wang; Shuai Tao; Chenjian Gu; Jie Ma; Youhua Xie; Yanfeng Liu

doi:10.1016/j.bbrc.2017.08.052

ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability

Biochem Biophys Res Commun. 2017 Oct 7;492(1):18-26. doi: 10.1016/j.bbrc.2017.08.052. Epub 2017 Aug 15.

Authors

Shenghao Wang¹, Li Tang², Junyu Lin³, Zhongliang Shen⁴, Yikun Yao⁵, Wei Wang³, Shuai Tao³, Chenjian Gu³, Jie Ma⁶, Youhua Xie⁷, Yanfeng Liu⁸

Affiliations

¹ Department of General Surgery, Huashan Hospital, Shanghai, China.
² Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
³ Key Laboratory of Medical Molecular Virology (MOE & MOH), Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
⁵ Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
⁶ Department of General Surgery, Huashan Hospital, Shanghai, China. Electronic address: jie.ma@fudan.edu.cn.
⁷ Key Laboratory of Medical Molecular Virology (MOE & MOH), Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: yhxie@fudan.edu.cn.
⁸ Department of General Surgery, Huashan Hospital, Shanghai, China. Electronic address: yanfengliu11@fudan.edu.cn.

PMID: 28821433
DOI: 10.1016/j.bbrc.2017.08.052

Abstract

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5⁺) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5^-) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma.

Keywords: ABCB5; Malignant melanoma initiating cells; Melanoma; Metastasis.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / deficiency
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
Animals
Cell Movement
Cells, Cultured
Humans
Male
Melanoma / metabolism*
Melanoma / pathology*
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis*
Neoplasms, Experimental / metabolism
Neoplasms, Experimental / pathology
Protein Stability
Transcription Factor RelA / metabolism*

Substances

ABCB5 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Transcription Factor RelA