STK11 mutation impacts CD1E expression to regulate the differentiation of macrophages in lung adenocarcinoma
Qingfeng Zhang1, Juan Feng2, Kui Liu1
1Department of Cardio-Thoracic Surgery, Zigong Fourth People's Hospital, Zigong, China.
Background:
The deficiency of serine/threonine protein kinase 11 (STK11), one of the most common tumor suppressor genes in non-small-cell lung cancer, is a crucial player in tumor immune microenvironment regulation. This study attempted to unveil how mutated STK11 impact the differentiation of macrophages in lung adenocarcinoma (LUAD).
Methods:
STK11 and CD1E expression levels in different cell models were assessed by quantitative reverse transcription polymerase chain reaction. Western blot was utilized to detect the protein expression levels of STK11, CD1E, apoptosis markers, and AMPK signaling pathway markers after transfection treatment. Cell viability and macrophage differentiation were detected by CCK-8 and flow cytometry. Immunohistochemistry and immunofluorescence were employed to detect the expression of related genes and macrophage markers, respectively.
Results:
This study found that STK11 mutations promoted the proliferation of LUAD cells and inhibited the differentiation of M1 macrophages, apoptosis, and the AMPK signaling pathway. Mutated STK11 led to CD1E downregulation, which curbed the differentiation of M1 macrophages and hence promoted LUAD progression. It was further validated by the in vivo experimental results that STK11 mutation significantly decreased the immune infiltration of M1 macrophages and promoted LUAD progression.
Conclusion:
It was revealed that STK11 mutation affected CD1E expression to regulate macrophage differentiation in LUAD and then promote tumor progression. In this way, CD1E could be a potential biological target for the therapeutic interventions of STK11-mutant LUAD patients. These findings also threw new light on a new therapeutic strategy for STK11-mutant tumor patients that assisted the macrophage polarization pathway.
Insights
Mutated serine/threonine protein kinase 11 (STK11) in lung adenocarcinoma promotes tumor growth by downregulating CD1E, inhibiting M1 macrophage differentiation. This suggests CD1E as a therapeutic target for STK11-mutant LUAD.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Serine/threonine protein kinase 11 (STK11) mutations are common in non-small-cell lung cancer and influence the tumor immune microenvironment.
- STK11 plays a critical role in regulating tumor progression and immune cell interactions.
Purpose of the Study:
- To investigate the impact of mutated STK11 on macrophage differentiation in lung adenocarcinoma (LUAD).
- To elucidate the molecular mechanisms by which STK11 mutations affect the tumor microenvironment and LUAD progression.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to assess STK11 and CD1E expression.
- Cell viability assays (CCK-8) and flow cytometry were employed to analyze macrophage differentiation and apoptosis.
- In vivo experiments, immunohistochemistry, and immunofluorescence were utilized to validate findings in a biological context.
Main Results:
- STK11 mutations were found to promote LUAD cell proliferation and inhibit M1 macrophage differentiation, apoptosis, and the AMPK signaling pathway.
- Mutated STK11 led to decreased CD1E expression, which impaired M1 macrophage differentiation and accelerated LUAD progression.
- In vivo studies confirmed that STK11 mutations reduced M1 macrophage infiltration and promoted tumor progression.
Conclusions:
- STK11 mutation influences CD1E expression to regulate macrophage differentiation in LUAD, thereby promoting tumor progression.
- CD1E emerges as a potential therapeutic target for STK11-mutant LUAD patients.
- The study highlights a novel therapeutic strategy targeting macrophage polarization for STK11-mutant tumors.
