Human endogenous retroviral K element encodes fusogenic activity in melanoma cells

Gengming Huang1, Zhongwu Li, Xiaohua Wan

  • 1Department of Pathology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA ; Sealy Center for Cancer Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.

Abstract

Insights

Human endogenous retroviruses (HERV K) proteins may drive melanoma cell fusion, creating multinuclear cells. Inhibiting HERV K reduced cell fusion, suggesting a role in melanoma progression and genetic changes.

Area of Science:

  • Oncology
  • Virology
  • Genetics

Background:

  • Human melanoma exhibits nuclear atypia with multinucleated cells.
  • Expression of the human endogenous retroviral K element (HERV K) is detected in these atypical melanoma cells.

Purpose of the Study:

  • To investigate the hypothesis that HERV K expression contributes to the formation of multinucleated atypical cells in melanoma.
  • To explore the role of HERV K in melanoma cell fusion and subsequent genetic alterations.

Main Methods:

  • HERV K expression was inhibited using RNA interference (RNAi) and monoclonal antibodies.
  • Melanoma cell fusion was assessed in vitro.
  • Loss of heterozygosity (LOH) analysis was performed on surviving cell clones.

Main Results:

  • Specific inhibition of HERV K significantly reduced intercellular fusion of cultured melanoma cells.
  • A cell clone that survived and proliferated after fusion exhibited loss of heterozygosity (LOH) at the D19S433 locus.
  • These findings suggest HERV K proteins mediate melanoma cell fusion.

Conclusions:

  • HERV K proteins play a role in mediating intercellular fusion of melanoma cells.
  • This fusion process may lead to the generation of multinucleated cells and drive the evolution of genetic changes.
  • Such genetic changes could confer growth and survival advantages to melanoma cells, promoting disease progression.

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