Therapeutic Potential of IBP As an Autophagy Inducer for Treating Lung Cancer Via Blocking PAK1/Akt/mTOR Signaling

Overview

Journal Mol Ther Oncolytics

Publisher Cell Press

Date 2021 Feb 12

PMID 33575473

Citations 10

Authors

Huimin Bu

Shirui Tan

Bo Yuan

Xiaomei Huang

Jiebang Jiang

Yejiao Wu

Jihong Jiang

Rongpeng Li

Affiliations

Soon will be listed here.

Abstract

Lung cancer is the most frequent and fatal malignancy in humans worldwide, yet novel successful drugs for control of this disease are still lacking. polysaccharides (IBPs) have been implicated in inhibiting diverse cancer types, but their functions in mitigating lung cancer are largely unknown. In this study, we identify a role of IBP in inhibiting lung cancer proliferation. We found that IBP significantly impedes the proliferation of lung cancer cells by inducing cytostatic macroautophagy both and . Mechanistically, IBP specifically promotes ubiquitination-mediated degradation of PAK1 (p21-activated kinase 1) and blocks its downstream Akt1/mTOR signaling pathway, leading to increased autophagic flux. In lung cancer xenografts in mice, IBP-induced cytostatic autophagy suppresses tumor development. Through site-directed mutational analysis, the underlying signaling augments ubiquitination via PAK1-ubiquitin interaction. Collectively, this work unravels the molecular mechanism underpinning IBP-induced cytostatic autophagy in lung cancer and characterizes IBP as a potential therapeutic agent for lung cancer treatment.

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