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

Autor: Chaudhary N; Cell and Tumor Biology and Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India., Joshi N; Cell and Tumor Biology and Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India., Doloi R; Cell and Tumor Biology and Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India., Shivashankar A; Cell and Tumor Biology and Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India., Thorat R; Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India., Dalal SN; Cell and Tumor Biology and Laboratory Animal Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India. Electronic address: sdalal@actrec.gov.in.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Sep 10; Vol. 620, pp. 1-7. Date of Electronic Publication: 2022 Jun 22.
DOI: 10.1016/j.bbrc.2022.06.060
Abstrakt: 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.
Competing Interests: Declaration of competing interest
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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