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SERPINB8 and furin regulate ITGAX expression and affect the proliferation and invasion of melanoma cells

Li Ni1, Pin Li2, Mingming Li1

  • 1Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Experimental Dermatology
|September 22, 2022
PubMed

Insights

Investigating ITGAX, SERPINB8, and furin in BRAF V600E mutant melanoma reveals that SERPINB8 and furin regulate ITGAX, a protein promoting melanoma cell proliferation and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Targeted therapy has revolutionized advanced melanoma treatment, yet challenges remain.
  • Understanding molecular mechanisms driving BRAF V600E mutant melanoma is crucial for therapeutic advancements.

Purpose of the Study:

  • To elucidate the roles and interactions of ITGAX, SERPINB8, and furin in BRAF V600E mutant melanoma.
  • To investigate how these factors influence melanoma cell behavior under BRAF inhibitor (BRAFi) treatment.

Main Methods:

  • Analysis of gene expression datasets (GSE141484, GSE22838) related to BRAF V600E mutation and BRAFi treatment.
  • In vitro experiments using A375 and 1205Lu melanoma cells treated with BRAF inhibitors (Vemurafenib, Dabrafenib).
  • Gene knockdown using siRNAs, cell proliferation assays (CCK-8), colony formation assays, invasion assays (Transwell), and immunoprecipitation.

Main Results:

  • BRAFi treatment downregulated ITGAX and SERPINB8 expression but did not affect furin levels.
  • Knockdown of ITGAX or SERPINB8 inhibited melanoma cell proliferation and invasion.
  • SERPINB8 knockdown decreased ITGAX expression, while furin inhibition or knockdown increased ITGAX protein levels.
  • SERPINB8 physically binds to furin.

Conclusions:

  • SERPINB8 and furin collaboratively regulate ITGAX expression in melanoma cells.
  • ITGAX significantly drives melanoma cell proliferation and invasion.
  • These findings offer insights into novel therapeutic targets for advanced melanoma.
Keywords:
BRAF V600E mutantintegrininvasionmelanoma

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