Upregulation of DJ-1 expression in melanoma regulates PTEN/AKT pathway for cell survival and migration

• Published in: Archives of Dermatological Research Vol. 313; no. 7; pp. 583 - 591
• Main Authors: Lee, Yoon Jin, Kim, Woo Il, Park, Tae Heum, Bae, Jin Ho, Nam, Hae Seon, Cho, Sung Woo, Choi, Young Jin, Lee, Sang Han, Cho, Moon Kyun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2021; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; BAX protein; Breast; Cancer; Caspase-3; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell survival; Cell Survival - genetics; Daxx protein; Dermatology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Invasiveness; Medicine; Medicine & Public Health; Melanoma; Melanoma - genetics; Melanoma - pathology; Melanoma - surgery; Metastases; Movement disorders; Neurodegenerative diseases; Original Paper; p53 Protein; PARK7 protein; Parkinson's disease; Phosphorylation; Phosphorylation - genetics; Poly(ADP-ribose) polymerase; Protein Deglycase DJ-1 - genetics; Protein Deglycase DJ-1 - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; Signal transduction; Signal Transduction - genetics; siRNA; Skin; Skin - pathology; Skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Skin Neoplasms - surgery; Thyroid; Tumor suppressor genes; Up-Regulation; PTEN; DJ-1; Migration; Melanoma; Apoptosis
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-020-02139-1

Cutaneous melanoma is known to be one of the most dangerous skin cancers because of its metastatic functions. Today, it is essential to investigate specific biomarkers for the target treatment in many diseases including cancers. DJ-1 protein, also known as Parkinson disease 7, has various functions associated with cancer progression including cell survival and migration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates the PI3K/AKT signaling pathway and its mutations have been reported to frequently occur in many cancers such as thyroid, breast and skin. Recently, DJ-1 has been identified as a negative regulator of PTEN in many human cancer cells. However, the impacts and relationship of DJ-1 and PTEN have not been studied yet in melanoma. To confirm the expression of DJ-1 and PTEN in melanoma compared to normal skin tissues and find out functions of DJ-1 in melanoma cells, Western blot analysis and immunohistochemical staining were used. Transfection of G361 cells with DJ-1-specific small interfering RNA was performed to figure out the roles of DJ-1 and the relationship between DJ-1 and PTEN in melanoma cells. In our study, the DJ-1 protein was significantly increased with loss of PTEN protein in melanoma compared to that in normal skin. Inhibition of DJ-1 in G361 cells induced apoptosis, and suppressed cell survival and migration. Furthermore, suppression of DJ-1 in G361 cells increased the expression of cleaved caspase-3, cleaved PARP, Bax, p53, and Daxx as well as PTEN, while it decreased expression of survivin, caspase-3, and PARP. Also, downregulated DJ-1 inhibited phosphorylation of AKT in G361 cells. Collectively, DJ-1 overexpression could affect the proliferative and invasive capabilities of melanoma cells via regulating the PTEN/AKT pathway and apoptosis-related proteins. This study suggests that DJ-1 may be a potential target for the treatment of melanoma.