Plakophilin3 loss leads to an increase in autophagy and radio-resistance

Autor:	Nazia Chaudhary, Neha Joshi, Rinki Doloi, Anusha Shivashankar, Rahul Thorat, Sorab N. Dalal
Rok vydání:	2022
Předmět:	Cell Line Tumor Neoplasms Biophysics Autophagy Humans Cell Biology Reactive Oxygen Species Molecular Biology Biochemistry Plakophilins Clone Cells
Zdroj:	Biochemical and biophysical research communications. 620
ISSN:	1090-2104
Popis:	Loss of the desmosomal plaque protein plakophilin3 (PKP3) leads to increased tumor progression and metastasis. As metastatic tumors are often resistant to therapy, we wished to determine whether PKP3 loss led to increased radioresistance. PKP3 knockdown cells showed increased resistance to radiation in vitro and in vivo. The increase in resistance was accompanied by an increased ability to clear reactive oxygen species (ROS) and increased autophagy. The increase in autophagy was required for radioresistance and ROS clearance as inhibiting autophagy using either chloroquine or knocking down ATG3 re-sensitized the PKP3 knockdown clones to radiotherapy. These experiments suggest that autophagy inhibitors could target therapy-resistant PKP3 deficient tumors.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a30150141d51656ea6f737f77ccf4983 https://pubmed.ncbi.nlm.nih.gov/35772211 Zobrazit plný text záznamu Full Text from ScienceDirect