IQGAP1 is an oncogenic target in canine melanoma

Becky H. Lee, Poornima H. Neela, Michael S Kent, Ashley M. Zehnder

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60%) or Nras (20%), human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

Original languageEnglish (US)
Article numbere0176370
JournalPLoS One
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2017

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melanoma
Canidae
Melanoma
Cells
dogs
mouth
Clustered Regularly Interspaced Short Palindromic Repeats
Peptides
mutation
Ports and harbors
Cell Line
Mutation
Infiltration
Scaffolds
cell lines
Chemical activation
peptides
Therapeutic Human Experimentation
Skin
neoplasms

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

IQGAP1 is an oncogenic target in canine melanoma. / Lee, Becky H.; Neela, Poornima H.; Kent, Michael S; Zehnder, Ashley M.

In: PLoS One, Vol. 12, No. 4, e0176370, 01.04.2017.

Research output: Contribution to journalArticle

Lee, Becky H. ; Neela, Poornima H. ; Kent, Michael S ; Zehnder, Ashley M. / IQGAP1 is an oncogenic target in canine melanoma. In: PLoS One. 2017 ; Vol. 12, No. 4.
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