Dataset Information

EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.

ABSTRACT: Cutaneous melanoma is one of the most common malignant skin tumors and advanced melanoma is usually associated with a poor prognosis. In the current study, we demonstrated the tumor suppressing role of epithelial membrane protein-2 (EMP2) by inducing apoptosis in a A375 human melanoma cell line. Mechanistically, the low expression of EMP2 in melanoma is partially due to autophagic protein degradation mediated by the mTOR pathway. These results suggest there is regulation of autophagy as well as EMP2 levels might be an interesting novel targeted therapeutic strategy for melanoma. Although the further investigation is needed to deeply understand the regulatory mechanisms of EMP2 in melanoma progression and metastasis, our results clarify the functions and mechanisms of autophagy in melanoma, and shed new light on novel targeted therapeutics for melanoma.

SUBMITTER: Wang M

PROVIDER: S-EPMC6636303 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.

Wang Manyi M Li Sijia S Zhang Peng P Wang Yujia Y Wang Chunting C Bai Ding D Jiang Xian X

Journal of Cancer 20190609 16

Cutaneous melanoma is one of the most common malignant skin tumors and advanced melanoma is usually associated with a poor prognosis. In the current study, we demonstrated the tumor suppressing role of epithelial membrane protein-2 (EMP2) by inducing apoptosis in a A375 human melanoma cell line. Mechanistically, the low expression of EMP2 in melanoma is partially due to autophagic protein degradation mediated by the mTOR pathway. These results suggest there is regulation of autophagy as well as ...[more]

PMID: 31333775

Similar Datasets

Project description:Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR)/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk), which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc) as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem/progenitor cells, suggesting that the role of Unk in neurogenesis may be conserved in mammals.

Dataset Information

EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.

Publications

EMP2 acts as a suppressor of melanoma and is negatively regulated by mTOR-mediated autophagy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets