ArticleThoracic cancer2020
CAPN1 promotes malignant behavior and erlotinib resistance mediated by phosphorylation of c-Met and PIK3R2 via degrading PTPN1 in lung adenocarcinoma.
Article in Thoracic cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
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- Circ-GSK3B up-regulates GSK3B to suppress the progression of lung adenocarcinoma.Cancer gene therapy · 2022Article
- Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer.Oxidative medicine and cellular longevity · 2022Article
- miRNA-451 regulates rhesus choroid-retinal endothelial cell function and proteome profile.International journal of ophthalmology · 2022Article
- Construction of a ferroptosis scoring system and identification of LINC01572 as a novel ferroptosis suppressor in lung adenocarcinoma.Frontiers in pharmacology · 2022Article
- Comprehensive analysis of prognostic value and immune infiltration of calpains in pancreatic cancer.Journal of gastrointestinal oncology · 2021Article
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- Low-intensity ultrasound inhibits melanoma cell proliferation in vitro and tumor growth in vivo.Journal of medical ultrasonics (2001) · 2021Article
- Integrating Multi-Omics Data for Gene-Environment Interactions.Biotech (Basel (Switzerland)) · 2021Article
- Prognosis and Characterization of Immune Microenvironment in Acute Myeloid Leukemia Through Identification of an Autophagy-Related Signature.Frontiers in immunology · 2021Article
- Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers.Frontiers in cell and developmental biology · 2021Article
- Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer.Drug design, development and therapy · 2021Article
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4 authors at 1 institution in 1 country.
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Abstract
backgroundCalpain 1 (CAPN1) has been found to be a promoter of cancer progression. PTPN1 as a physiological target molecule of CAPN1 plays a dephosphorylated role on multiple receptor tyrosine kinases. This study aimed to reveal the effects of CAPN1/PTPN1 on malignant phenotype and EGFR-TKI resistance of lung adenocarcinoma (LUAD) cells.
methodsA total of 84 primary LUAD tissues and paired paracancerous normal tissues were collected. Quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) methods were used to measure the expression of CAPN1 and PTPN1 in tissues. qRT-PCR and western blot were used to detect the expressions of CAPN1, PTPN1, c-Met and PIK3R2 in cell lines. Cell counting kit-8 (CCK-8), colony formation and transwell assay were carried out to evaluate cell erlotinib resistance, proliferation, migration and invasion. Co-IP assay was used to verify the interaction between proteins. Cycloheximide (CHX) was applied to block protein synthesis.
resultsCAPN1, c-Met and PIK3R2 were significantly upregulated and the correlation was positive in LUAD, while PTPN1 was decreased. EGFR-sensitive mutation was related to CAPN1/PTPN1. in vitro studies showed that PTPN1 can mediate dephosphorylation of c-Met and PIK3R2 by binding with both, thereby weakening cell proliferation, metastasis and erlotinib resistance, while CAPN1 could enhance the degradation of PTPN1 protein as a cancer promoter.
conclusionsCAPN1 enhances the malignant behavior and erlotinib resistance of LUAD cells via degrading PTPN1 and then activating c-Met/PIK3R2, which suggests CAPN1/PTPN1 may serve as tumor markers or potential targets for diagnosis and treatment of LUAD. KEY POINTS: Significant findings of the study Superior CAPN1 and inferior PTPN1 were related to activation of c-Met/PIK3R2 in lung adenocarcinoma. Moreover, regulations of CAPN1 and PTPN1 induced the changes of malignant behavior and erlotinib resistance. What this study adds Our findings confirmed that CAPN1/PTPN1 play crucial roles on proliferation, metastasis and erlotinib resistance of LUAD cells as c-Met/PIK3R2 regulators, and validated the regulatory mechanism of CAPN1 on PTPN1 in tumor model for the first time.
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