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Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma

Authors: Wiedemann, Gabriela; Aithal, Celina; Kraechan, Angelina; Heise, Constanze; Cadilha, Bruno; Zhang, Jin; Duewell, Peter; +4 Authors

Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma

Abstract

Microphthalmia-associated transcription factor (MITF) is a key transcription factor in melanoma development and progression. MITF amplification and downregulation have been observed in a significant proportion of melanoma patients and correlate with clinical outcomes. Here, we have investigated the effect of MITF on melanoma chemokine expression and immune cell attraction. In B16F10 melanoma cells, MITF knockdown reduced expression of CXCL10, with concomitantly decreased attraction of immune cells and accelerated tumor outgrowth. Conversely, overexpression of MITF in YUMM1.1 melanoma cells also led to an increased immune cell attraction in vitro. Subcutaneous YUMM1.1 melanomas overexpressing MITF however showed a reduced immune infiltration of lymphocytes and an increased tumor growth. In human melanoma cell lines, silencing of MITF enhanced chemokine production and immune cell attraction, while overexpression of MITF led to lower immune cell attraction. In summary, our results show that MITF regulates chemokine expression in murine and in human melanoma cells, and affects in vivo immune cell attraction and tumor growth. These results reveal a functional relationship between MITF and immune cell infiltration, which may be exploited for cancer therapy.

Country
France
Keywords

Original article, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

  • BIP!
    Impact byBIP!
    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    30
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
30
Top 10%
Top 10%
Top 10%
Green
gold
Related to Research communities
Cancer Research