Open AccessCritical role of glioma‐associated oncogene homolog 1 in maintaining invasive and mesenchymal‐like properties of melanoma cells
Author(s) -
Gunarta I Ketut,
Li Rong,
Nakazato Ryota,
Suzuki Ryusuke,
Boldbaatar Jambaldorj,
Suzuki Takeshi,
Yoshioka Katsuji
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13294
Subject(s) - microphthalmia associated transcription factor , melanoma , cancer research , epithelial–mesenchymal transition , gli1 , transcription factor , biology , oncogene , mesenchymal stem cell , gene knockdown , carcinogenesis , metastasis , small hairpin rna , cancer , hedgehog signaling pathway , cell culture , microbiology and biotechnology , signal transduction , cell cycle , genetics , gene
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non‐invasive and invasive potential, and microphthalmia‐associated transcription factor ( MITF ) is known to play a central role in this process. The transcription factor glioma‐associated oncogene homolog 1 ( GLI 1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI 1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear. Here we investigated whether and how GLI 1 is involved in the invasive ability of melanoma cells. Gli1 knockdown ( KD ) melanoma cell lines, established by using Gli1 ‐targeting lentiviral short hairpin RNA , exhibited a markedly reduced invasion ability, but their MITF expression and activity were the same as controls. Gli1 KD melanoma cells also led to less lung metastasis in mice compared with control melanoma cells. Furthermore, the Gli1 KD melanoma cells underwent a mesenchymal‐to‐epithelial‐like transition, accompanied by downregulation of the epithelial‐to‐mesenchymal transition ( EMT )‐inducing transcription factors ( EMT ‐ TF ) Snail1 , Zeb1 and Twist1 , but not Snail2 or Zeb2 . Collectively, these results indicate that GLI 1 is important for maintaining the invasive and mesenchymal‐like properties of melanoma cells independent of MITF , most likely by modulating a subset of EMT ‐ TF . Our findings provide new insight into how heterogeneity and plasticity are achieved and regulated in melanoma.