STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway

Jørgen Sikkeland; Matthew Yoke Wui Ng; Hatice Zeynep Nenseth; Bilal Unal; Su Qu; Yang Jin; Anne Simonsen; Fahri Saatcioglu

STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway

Am J Cancer Res. 2022 Jan 15;12(1):327-336. eCollection 2022.

Authors

Jørgen Sikkeland¹, Matthew Yoke Wui Ng^{1

2}, Hatice Zeynep Nenseth^{1

3}, Bilal Unal³, Su Qu¹, Yang Jin^{1

3}, Anne Simonsen^{2

4}, Fahri Saatcioglu^{1

3}

Affiliations

¹ Department of Biosciences, University of Oslo Postboks 1066 Blindern, Oslo 0316, Norway.
² Department of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo Oslo 0313, Norway.
³ Institute for Cancer Genetics and Informatics, Oslo University Hospital Oslo 0310, Norway.
⁴ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital Montebello, Oslo 0379, Norway.

PMID: 35141021
PMCID: PMC8822275

Abstract

Six Transmembrane Protein of Prostate 2 (STAMP2) is critical for prostate cancer (PCa) growth. We previously showed that STAMP2 regulates the expression of stress induced transcription factor ATF4, which is implicated in starvation-induced autophagy. We therefore investigated whether STAMP2 is involved in the regulation of autophagy in PCa cells. Here we show that STAMP2 suppresses autophagy in PCa cells through modulation of the integrated stress response axis. We also find that STAMP2 regulates mitochondrial respiration. These findings suggest that STAMP2 has significant metabolic effects through mitochondrial function and autophagy, both of which support PCa growth.

Keywords: ATF4; Prostate cancer; STAMP2; autophagy; eIF2α; integrated stress response; mitochondria.