Upregulation of DJ-1 expression in melanoma regulates PTEN/AKT pathway for cell survival and migration
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ORIGINAL PAPER
Upregulation of DJ‑1 expression in melanoma regulates PTEN/AKT pathway for cell survival and migration Yoon Jin Lee1 · Woo Il Kim2 · Tae Heum Park2 · Jin Ho Bae2 · Hae Seon Nam1 · Sung Woo Cho1 · Young Jin Choi1 · Sang Han Lee1 · Moon Kyun Cho2 Received: 9 August 2019 / Revised: 25 March 2020 / Accepted: 12 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 apoptosisrelated proteins. This study suggests that DJ-1 may be a potential target for the treatment of melanoma. Keywords DJ-1 · PTEN · Melanoma · Apoptosis · Migration
Introduction In patients with cutaneous melanoma induced by carcinogenesis of melanocytes, metastases to distant organs are common compared to other skin cancers [1]. Although targeted therapies, immunotherapies, and new strategies for early diagnosis and prevention have been developed, most patients with melanoma still have poor prognoses when it becomes metastatic [2]. Invasive melanoma accounts for * Moon Kyun Cho [email protected] 1
Molecular Cancer Research, Soonchunhyang University College of Medicine, Cheonan‑si 31151, Republic of Korea
Department of Dermatology, Soonchunhyang University Hospital, 59 Daesahwan‑ro, Yongsan‑gu, Seoul
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