βKlotho is identified as a target for theranostics in non-small cell lung cancer
Fan Li1, Xiyao Li1, Ziming Li2
1State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Non-small cell lung cancer (NSCLC) remains a great challenge, calling for the identification of novel molecular targets with diagnostic/therapeutic value. Here, we sought to characterize the expression of βKlotho and its anti-tumor roles in NSCLC. Methods: The expression of βKlotho was examined in NSCLC cells and tissues by western blot, qRT-PCR and immunohistochemistry staining respectively. Biological roles of βKlotho were revealed by a series of functional in vitro and in vivo studies. Serum βKlotho concentrations of patients were measured using specific ELISA methods. Results: Serum βKlotho concentrations of NSCLC patients were significantly lower than the control group. Moreover, βKlotho expression was negatively associated with lymph node metastasis, overall survival and progression-free survival. Overexpression of βKlotho or exogenous βKlotho administration inhibited the proliferation and migration of NSCLC cells, accompanied by induction of apoptosis, G1 to S phase arrest, and inactivation of ERK1/2, AKT and STAT3 signaling. Furthermore, βKlotho overexpression inhibited NSCLC tumor growth in vivo. Conclusions: βKlotho serves as a novel target for theranostics in NSCLC, which has potential clinical applications in the future.
Insights
Lower serum levels of βKlotho were found in non-small cell lung cancer (NSCLC) patients. βKlotho inhibits NSCLC progression and may offer new diagnostic and therapeutic strategies for this challenging disease.
Area of Science:
- Oncology
- Molecular Biology
Background:
- Non-small cell lung cancer (NSCLC) presents significant challenges, necessitating the discovery of novel molecular targets for diagnosis and therapy.
- βKlotho is a protein whose role in NSCLC is not well understood.
Purpose of the Study:
- To investigate the expression patterns of βKlotho in NSCLC.
- To elucidate the anti-tumor functions of βKlotho in NSCLC.
- To assess the potential of βKlotho as a theranostic target in NSCLC.
Main Methods:
- Western blot, qRT-PCR, and immunohistochemistry were used to examine βKlotho expression in NSCLC cells and tissues.
- In vitro and in vivo functional studies assessed the biological roles of βKlotho.
- Serum βKlotho concentrations were quantified using ELISA in NSCLC patients.
Main Results:
- NSCLC patients exhibited significantly lower serum βKlotho concentrations compared to controls.
- βKlotho expression inversely correlated with lymph node metastasis, overall survival, and progression-free survival.
- Overexpression or administration of βKlotho suppressed NSCLC cell proliferation and migration, induced apoptosis, caused G1-S phase arrest, and inactivated ERK1/2, AKT, and STAT3 signaling pathways. In vivo studies confirmed tumor growth inhibition.
Conclusions:
- βKlotho demonstrates significant anti-tumor activity in NSCLC.
- βKlotho represents a promising novel target for theranostics in NSCLC.
- βKlotho holds potential for future clinical applications in NSCLC management.
