Erratum

Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ

Keiji Tanese, Yuuri Hashimoto, Zuzana Berkova, Yuling Wang, Felipe Samaniego, Jeffrey E. Lee, Suhendan Ekmekcioglu, Elizabeth A. Grimm

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Melanoma is believed to be a highly immunogenic tumor and recent developments in immunotherapies are promising. IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. CD74 was highly expressed in melanoma tissues. Moreover, the expression of CD74 on tumor cells correlated with plasma IFN-γ levels in melanoma patient samples. In our analysis of melanoma cell lines, all produced MIF constitutively. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling, suggesting that targeting the CD74-MIF interaction under IFN-γ-stimulatory conditions would be an effective therapeutic approach for melanoma.

Original languageEnglish
Pages (from-to)2775-2784
Number of pages10
JournalJournal of Investigative Dermatology
Volume135
Issue number11
DOIs
Publication statusPublished - 2015 Nov 1

Fingerprint

Interferons
Tumors
Melanoma
Cells
Survival
Phosphorylation
Macrophage Migration-Inhibitory Factors
Neoplasms
Interleukin-8
Phosphatidylinositol 3-Kinases
Heterografts
Interleukin-6
Cell Line
Tissue
Ligands
Plasmas
Molecules
Immunotherapy
Cell Survival
Growth

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Erratum : Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ. / Tanese, Keiji; Hashimoto, Yuuri; Berkova, Zuzana; Wang, Yuling; Samaniego, Felipe; Lee, Jeffrey E.; Ekmekcioglu, Suhendan; Grimm, Elizabeth A.

In: Journal of Investigative Dermatology, Vol. 135, No. 11, 01.11.2015, p. 2775-2784.

Research output: Contribution to journalArticle

Tanese, K, Hashimoto, Y, Berkova, Z, Wang, Y, Samaniego, F, Lee, JE, Ekmekcioglu, S & Grimm, EA 2015, 'Erratum: Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ', Journal of Investigative Dermatology, vol. 135, no. 11, pp. 2775-2784. https://doi.org/10.1038/jid.2015.204
Tanese, Keiji ; Hashimoto, Yuuri ; Berkova, Zuzana ; Wang, Yuling ; Samaniego, Felipe ; Lee, Jeffrey E. ; Ekmekcioglu, Suhendan ; Grimm, Elizabeth A. / Erratum : Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 11. pp. 2775-2784.
@article{c485e66f37e245e78241225a42e2efc3,
title = "Erratum: Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ",
abstract = "Melanoma is believed to be a highly immunogenic tumor and recent developments in immunotherapies are promising. IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. CD74 was highly expressed in melanoma tissues. Moreover, the expression of CD74 on tumor cells correlated with plasma IFN-γ levels in melanoma patient samples. In our analysis of melanoma cell lines, all produced MIF constitutively. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling, suggesting that targeting the CD74-MIF interaction under IFN-γ-stimulatory conditions would be an effective therapeutic approach for melanoma.",
author = "Keiji Tanese and Yuuri Hashimoto and Zuzana Berkova and Yuling Wang and Felipe Samaniego and Lee, {Jeffrey E.} and Suhendan Ekmekcioglu and Grimm, {Elizabeth A.}",
year = "2015",
month = "11",
day = "1",
doi = "10.1038/jid.2015.204",
language = "English",
volume = "135",
pages = "2775--2784",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Erratum

T2 - Cell Surface CD74-MIF Interactions Drive Melanoma Survival in Response to Interferon-γ

AU - Tanese, Keiji

AU - Hashimoto, Yuuri

AU - Berkova, Zuzana

AU - Wang, Yuling

AU - Samaniego, Felipe

AU - Lee, Jeffrey E.

AU - Ekmekcioglu, Suhendan

AU - Grimm, Elizabeth A.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Melanoma is believed to be a highly immunogenic tumor and recent developments in immunotherapies are promising. IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. CD74 was highly expressed in melanoma tissues. Moreover, the expression of CD74 on tumor cells correlated with plasma IFN-γ levels in melanoma patient samples. In our analysis of melanoma cell lines, all produced MIF constitutively. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling, suggesting that targeting the CD74-MIF interaction under IFN-γ-stimulatory conditions would be an effective therapeutic approach for melanoma.

AB - Melanoma is believed to be a highly immunogenic tumor and recent developments in immunotherapies are promising. IFN-γ produced by immune cells has a crucial role in tumor immune surveillance; however, it has also been reported to be pro-tumorigenic. In the current study, we found that IFN-γ enhances the expression of CD74, which interacts with its ligand, macrophage migration inhibitory factor (MIF), and thereby activates the PI3K/AKT pathway in melanoma, promoting tumor survival. IFN-γ increased phosphorylation of AKT Ser473 and upregulated total cell surface expression of CD74 in human melanoma cell lines tested. CD74 was highly expressed in melanoma tissues. Moreover, the expression of CD74 on tumor cells correlated with plasma IFN-γ levels in melanoma patient samples. In our analysis of melanoma cell lines, all produced MIF constitutively. Blockade of CD74-MIF interaction reduced AKT phosphorylation and expression of pro-tumorigenic molecules, including IL-6, IL-8, and BCL-2. Inhibition of CD74-MIF interaction significantly suppressed tumor growth in the presence of IFN-γ in our xenograft mouse model. Thus, we conclude that IFN-γ promotes melanoma cell survival by regulating CD74-MIF signaling, suggesting that targeting the CD74-MIF interaction under IFN-γ-stimulatory conditions would be an effective therapeutic approach for melanoma.

UR - http://www.scopus.com/inward/record.url?scp=84947019270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947019270&partnerID=8YFLogxK

U2 - 10.1038/jid.2015.204

DO - 10.1038/jid.2015.204

M3 - Article

VL - 135

SP - 2775

EP - 2784

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 11

ER -