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Selenoprotein K functions to promote melanoma progression and metastasis
Author(s) -
Hoffmann Peter,
Marciel Michael,
Kilicasian Pascal,
Pham Andrew,
Hoffmann FuKun
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.802.13
Subject(s) - melanoma , cancer research , in vivo , cell culture , lymph , biology , genetically modified mouse , metastasis , transgene , microbiology and biotechnology , pathology , cancer , medicine , gene , genetics
We have found that selenoprotein K (Selenok) is crucial for calcium flux in immune cells, but had not investigated its role in cancer cells. A recent study showed that calcium flux was important for melanoma cells to proliferate and migrate. Thus, we set out to determine if Selenok plays an important role in melanoma using in vitro and in vivo models. Analyses of four different NCI‐60 human melanoma cell lines found that Selenok levels varied in these cells and one cell line in particular, SK‐Mel28, was subjected to CRISPR/Cas9 genome editing to mutate Selenok. Mutating wild‐type (WT Selenok) to a truncated version (Trunc Selenok) led to reduced calcium flux, migration using a scratch assay, and lower colony formation. These functions were rescued with a plasmid expressing GFP‐Selenok but not with GFP alone. An established transgenic mouse strain, Grm1‐Tg, develops spontaneous melanoma that metastasizes to lymph nodes at 4 months of age and was crossed with Selenok KO mice to generate the following: GRM1‐Tg/Selenok−/−, GRM1‐Tg/Selenok−/+, GRM1‐Tg/Selenok+/+. These littermates allowed us to determine how loss of one or both or none of Selenok alleles on the Grm1‐Tg background affected progression and metastasis of melanoma in vivo. We used both male and female mice and results showed that lack of Selenok expression in GRM1‐Tg/Selenok−/− mice led to lower primary tumors on tails and ears and less melanoma cells in draining lymph nodes. The presence of one or two Selenok alleles were similar and showed significantly higher levels of melanoma and metastasis. Overall, these results suggest that melanoma cells require Selenok expression for primary tumor growth and metastasis to other tissues. Support or Funding Information We sincerely thank Ann Hashimoto for her hard work in maintaining mouse colonies for this study. This research was supported by NIH grant R01AI089999, and core facilities supported by P30GM114737, P30GM103341, G12RR003061, G12MD007601.