FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer.

Cell Death Dis

Department of Breast Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P. R. China.

Published: October 2020

AI Article Synopsis

  • Polyamine biosynthesis is crucial for cell growth in non-small-cell lung cancer (NSCLC), and the novel gene FATS is linked to this process.
  • FATS is significantly downregulated in NSCLC tissues, correlating with poorer survival rates, and its presence triggers cell death through pro-death autophagy.
  • FATS also suppresses polyamine synthesis by inhibiting the enzyme ornithine decarboxylase, involving binding to the estrogen receptor, thus highlighting its potential role in NSCLC progression.

Article Abstract

Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERβ and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547721PMC
http://dx.doi.org/10.1038/s41419-020-03052-1DOI Listing

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