Related Experiment Video
Updated: Aug 20, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
A Novel TP53 Gene Mutation Sustains Non-Small Cell Lung Cancer through Mitophagy
Yuanli Wang1,2, Kah Yong Goh3, Zhencheng Chen1
1School of Life and Environmental Sciences, Guilin University of Electronic Technology, Guilin 541014, China.
Abstract:
Lung cancer is the leading cause of cancer death in the world. In particular, non-small-cell lung cancer (NSCLC) represents the majority of the lung cancer population. Advances in DNA sequencing technologies have significantly contributed to revealing the roles, functions and mechanisms of gene mutations. However, the driver mutations that cause cancers and their pathologies remain to be explored. Here, we performed next-generation sequencing (NGS) on tumor tissues isolated from 314 Chinese NSCLC patients and established the mutational landscape in NSCLC. Among 656 mutations, we identified TP53-p.Glu358Val as a driver mutation in lung cancer and found that it activates mitophagy to sustain cancer cell growth. In support of this finding, mice subcutaneously implanted with NSCLC cells expressing TP53-p.Glu358Val developed larger tumors compared to wild-type cells. The pharmaceutical inhibition of autophagy/mitophagy selectively suppresses the cell proliferation of TP53-null or TP53-p.Glu358Val-expressing lung cancer cells. Together, our study characterizes a new TP53 mutation identified from Chinese lung cancer patients and uncovers its roles in regulating mitophagy, providing a new insight into NSCLC treatment.
Insights
Researchers identified a new TP53 mutation (TP53-p.Glu358Val) in non-small cell lung cancer (NSCLC) that drives tumor growth by activating mitophagy. Inhibiting this process may offer a new NSCLC treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide.
- Understanding driver mutations is crucial for developing targeted therapies.
- Next-generation sequencing (NGS) aids in identifying genetic alterations in cancer.
Purpose of the Study:
- To identify novel driver mutations in NSCLC using NGS.
- To investigate the functional role of identified mutations in cancer progression.
- To explore potential therapeutic strategies targeting identified mutations.
Main Methods:
- Next-generation sequencing (NGS) of tumor tissues from 314 Chinese NSCLC patients.
- In vitro and in vivo experiments using NSCLC cell lines and mouse models.
- Pharmacological inhibition of autophagy/mitophagy pathways.
Main Results:
- Identified TP53-p.Glu358Val as a driver mutation in NSCLC among 656 mutations.
- TP53-p.Glu358Val activates mitophagy, promoting cancer cell growth and tumor development in mice.
- Targeted inhibition of autophagy/mitophagy suppressed proliferation in TP53-mutated NSCLC cells.
Conclusions:
- Characterized a novel TP53 mutation (TP53-p.Glu358Val) in Chinese NSCLC patients.
- Established the role of TP53-p.Glu358Val in activating mitophagy for cancer cell survival.
- Suggests targeting mitophagy as a potential therapeutic approach for NSCLC.
More Related Videos
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
09:13Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
Published on: August 12, 2018
Related Concept Videos
02:23Abnormal Proliferation
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:37DNA Damage can Stall the Cell Cycle
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...