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PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy.
Autophagy. 2020 07; 16(7):1236-1247.A

Abstract

Macroautophagy/autophagy is an evolutionarily conserved intracellular process that recycles and degrades intracellular components to sustain homeostasis in response to deficiency of nutrients or growth factors. PAQR3 is a newly discovered tumor suppressor that also regulates autophagy induced by nutrient starvation via AMPK and MTORC1 signaling pathways. In this study, we investigated whether PAQR3 modulates EGFR-mediated autophagy and whether such regulation is associated with the tumor suppressive activity of PAQR3. PAQR3 is able to inhibit the in vitro and in vivo growth of non-small cell lung cancer (NSCLC) cells. PAQR3 potentiates autophagy induced by EGFR inhibitor erlotinib. Knockdown of PAQR3 abrogates erlotinib-mediated reduction of BECN1 interaction with autophagy inhibitory proteins RUBCN/Rubicon and BCL2. PAQR3 blocks the interaction of BECN1 with the activated form of EGFR and inhibits tyrosine phosphorylation of BECN1. Furthermore, inhibition of autophagy by knocking down ATG7 abrogates the tumor suppressive activity of PAQR3 in NSCLC cells. Collectively, these data indicate that PAQR3 suppresses tumor progression of NSCLC cells through modulating EGFR-regulated autophagy.

ABBREVIATIONS

AKT: thymoma viral proto-oncogene; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1; CCK-8: cell counting kit-8; CQ: chloroquine diphosphate; DMEM: Dulbecco's modified Eagle's medium; EdU: 5-ethynyl-2'-deoxyuridine; EGFR: epidermal growth factor receptor; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; IgG: Immunoglobulin G; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; MTT: thiazolyl blue tetrazolium bromide; NSCLC: Non-small cell lung cancer; MAP2K/MEK: mitogen-activated protein kinase kinase; MAPK/ERK: mitogen-activated protein kinase; PAQR3: progestin and adipoQ receptor family member 3; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PRKAA/AMPK: protein kinase, AMP-activated alpha catalytic; RUBCN: rubicon autophagy regulator; RPS6: ribosomal protein S6; RAS: Ras proto-oncogene; RAF: Raf proto-oncogene; TKI: tyrosine kinase inhibitor; TUBA4A: tubulin alpha 4a; UVRAG: UV radiation resistance associated.

Authors+Show Affiliations

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China.CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China. School of Life Sciences and Technology, Shanghai Tech University , Shanghai, China.CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China. School of Life Sciences and Technology, Shanghai Tech University , Shanghai, China.China Animal Health and Epidemiology Center , Qingdao, Shandong, China.CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China. School of Life Sciences and Technology, Shanghai Tech University , Shanghai, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31448672

Citation

Cao, Qianqian, et al. "PAQR3 Suppresses the Growth of Non-small Cell Lung Cancer Cells Via Modulation of EGFR-mediated Autophagy." Autophagy, vol. 16, no. 7, 2020, pp. 1236-1247.
Cao Q, You X, Xu L, et al. PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy. Autophagy. 2020;16(7):1236-1247.
Cao, Q., You, X., Xu, L., Wang, L., & Chen, Y. (2020). PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy. Autophagy, 16(7), 1236-1247. https://doi.org/10.1080/15548627.2019.1659654
Cao Q, et al. PAQR3 Suppresses the Growth of Non-small Cell Lung Cancer Cells Via Modulation of EGFR-mediated Autophagy. Autophagy. 2020;16(7):1236-1247. PubMed PMID: 31448672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy. AU - Cao,Qianqian, AU - You,Xue, AU - Xu,Lijiao, AU - Wang,Lin, AU - Chen,Yan, Y1 - 2019/08/30/ PY - 2019/8/27/pubmed PY - 2021/7/28/medline PY - 2019/8/27/entrez KW - ATG7 KW - BECN1 KW - EGFR KW - autophagy KW - lung cancer KW - tumor suppressor SP - 1236 EP - 1247 JF - Autophagy JO - Autophagy VL - 16 IS - 7 N2 - : Macroautophagy/autophagy is an evolutionarily conserved intracellular process that recycles and degrades intracellular components to sustain homeostasis in response to deficiency of nutrients or growth factors. PAQR3 is a newly discovered tumor suppressor that also regulates autophagy induced by nutrient starvation via AMPK and MTORC1 signaling pathways. In this study, we investigated whether PAQR3 modulates EGFR-mediated autophagy and whether such regulation is associated with the tumor suppressive activity of PAQR3. PAQR3 is able to inhibit the in vitro and in vivo growth of non-small cell lung cancer (NSCLC) cells. PAQR3 potentiates autophagy induced by EGFR inhibitor erlotinib. Knockdown of PAQR3 abrogates erlotinib-mediated reduction of BECN1 interaction with autophagy inhibitory proteins RUBCN/Rubicon and BCL2. PAQR3 blocks the interaction of BECN1 with the activated form of EGFR and inhibits tyrosine phosphorylation of BECN1. Furthermore, inhibition of autophagy by knocking down ATG7 abrogates the tumor suppressive activity of PAQR3 in NSCLC cells. Collectively, these data indicate that PAQR3 suppresses tumor progression of NSCLC cells through modulating EGFR-regulated autophagy. ABBREVIATIONS: AKT: thymoma viral proto-oncogene; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1; CCK-8: cell counting kit-8; CQ: chloroquine diphosphate; DMEM: Dulbecco's modified Eagle's medium; EdU: 5-ethynyl-2'-deoxyuridine; EGFR: epidermal growth factor receptor; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; IgG: Immunoglobulin G; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; MTT: thiazolyl blue tetrazolium bromide; NSCLC: Non-small cell lung cancer; MAP2K/MEK: mitogen-activated protein kinase kinase; MAPK/ERK: mitogen-activated protein kinase; PAQR3: progestin and adipoQ receptor family member 3; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PRKAA/AMPK: protein kinase, AMP-activated alpha catalytic; RUBCN: rubicon autophagy regulator; RPS6: ribosomal protein S6; RAS: Ras proto-oncogene; RAF: Raf proto-oncogene; TKI: tyrosine kinase inhibitor; TUBA4A: tubulin alpha 4a; UVRAG: UV radiation resistance associated. SN - 1554-8635 UR - https://www.unboundmedicine.com/medline/citation/31448672/PAQR3_suppresses_the_growth_of_non_small_cell_lung_cancer_cells_via_modulation_of_EGFR_mediated_autophagy_ DB - PRIME DP - Unbound Medicine ER -