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Two‐pore channel 2 (TPC2) Role in Melanoma
Author(s) -
Hanbashi Ali,
D'Amore Antonella,
Parrington John
Publication year - 2020
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.2020.34.s1.04762
Subject(s) - crispr , melanoma , biology , cancer , cancer research , angiogenesis , melanin , cas9 , cancer cell , cell culture , gene silencing , microbiology and biotechnology , computational biology , biochemistry , genetics , gene
Two‐pore channels (TPC), a recently described class of NAADP‐ and PI(3,5)P2–sensitive calcium‐permeable cation channels in the endolysosomal system of cells have a crucial rule in cellular functions and have been linked to various type of diseases including cancer. Here, TPC2 protein stable silencing in melanoma cancer cell lines was developed using CRISPR/Cas9 genome editing technology. TPC2 knockout (KO) in B16 murine melanoma cancer cell was associated with higher viability and migration rates with higher melanin accumulation inside the cells compared to wild type controls. TPC2 KO CHL1 human melanoma cancer cells showed an increased level of proliferation with reduced migration capacity. Both KO cell lines had lower invasion rates and lacked capacity for angiogenesis compared to wild type controls. Proteomic analysis was used to identify novel targets which were affected by genetic modification of TPC2. Thus, the findings of the present study indicated that CRISPR/Cas9 model is an ideal and cost‐effective tool to study the role of TPC2 in melanoma cancer cells which can be further used as a target to understand the biological basis of this disease. Support or Funding Information Royal Embassy of Saudi Arabia Cultural Bureau