The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling

Arivazhagan, Roshini; Goparaju, Chandra; Kundu, Somanath; Nandhu, Mohan S.; Longo, Sharon L.; Longo, John A.; Chou, Joan; Middleton, Frank A.; Pass, Harvey I.; Viapiano, Mariano S.

doi:10.3389/fonc.2022.1014749

Cited by 4 publications

(3 citation statements)

References 62 publications

(97 reference statements)

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“…The pathway has also been linked to OS development [7,8,[25][26][27] and XN has been shown to promote apoptosis through inhibiting PI3K/AKT/mTOR-kinase in gastric cancer [28]. Furthermore, EFEMP1 can promote the growth of pleural mesothelioma by action of PI3K/Akt signaling [29]. Here, the inhibitory effects of XN/EFEMP1 on OS were found to be mediated by PI3K/AKT.…”

Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits osteosarcoma proliferation, migration, and invasion via EFEMP1/PI3K/AKT axis

Wang,

Yan,

et al. 2024

Preprint

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Background Osteosarcoma (OS) is a tumor of bone. Xanthohumol (XN) has been found to have antitumor effects. However, it is not known whether XN can prevent the development of OS. Method The malignant phenotypes of OS cell lines were evaluated using CCK-8, clone-formation, EdU, Transwell, and wound-healing assays. The molecular mechanism of XN action was investigated by transcriptome sequencing. mRNA levels in OS cells were examined by q-PCR and protein by western blotting and immunofluorescence, while Ki-67 and PCNA levels in tumors were assessed using immunohistochemistry. Results XN dose-dependently blocked proliferation, migration, and invasion in OS cell lines. Transcriptome sequencing revealed that EFEMP1 expression was significantly reduced after XN treatment, which was shown by rescue assays to have a tumor-suppressive effect. Reduced levels of EFEMP1/PI3K/AKT axis after XN treatment were demonstrated by western blotting. Conclusion XN blocks OS tumorigenic behavior by inhibition of the EFEMP1/PI3K/AKT axis.

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Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits osteosarcoma proliferation, migration, and invasion via EFEMP1/PI3K/AKT axis

Wang,

Yan,

et al. 2024

Preprint

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“…As a member of the fibulin family (extracellular glycoproteins), Fibulin-3 has been linked to cell proliferation and migration through the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP-1) gene ( 114 ). From 32,000 probe IDs evaluated with the HG1 Affymetrix array, 48 MPMs with matching normal peritoneum showed a 7-fold increase (P=10 -9 ) in EFEMP1 RNA expression ( 100 ).…”

Section: Multiple Therapies For Mesothelioma Managementmentioning

confidence: 99%

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

et al. 2023

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The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.

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“…Fibulin-3 has also been proposed as a relevant molecular target to reduce PM progression, and anti-fibulin-3 approaches are being studied [88].…”

Section: Fibulin-3mentioning

confidence: 99%

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers

Sorino,

Mondoni,

Marchetti

et al. 2023

JCM

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Pleural mesothelioma (PM) is a type of cancer that is highly related to exposure to asbestos fibers. It shows aggressive behavior, and the current therapeutic approaches are usually insufficient to change the poor prognosis. Moreover, apart from staging and histological classification, there are no validated predictors of its response to treatment or its long-term outcomes. Numerous studies have investigated minimally invasive biomarkers in pleural fluid or blood to aid in earlier diagnosis and prognostic assessment of PM. The most studied marker in pleural effusion is mesothelin, which exhibits good specificity but low sensitivity, especially for non-epithelioid PM. Other biomarkers found in pleural fluid include fibulin-3, hyaluronan, microRNAs, and CYFRA-21.1, which have lower diagnostic capabilities but provide prognostic information and have potential roles as therapeutic targets. Serum is the most investigated matrix for biomarkers of PM. Several serum biomarkers in PM have been studied, with mesothelin, osteopontin, and fibulin-3 being the most often tested. A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker in patients with suspected mesothelioma. With different serum and pleural fluid cut-offs, it provides useful information on the diagnosis, prognosis, follow-up, and response to therapy in epithelioid PM. Panels combining different markers and proteomics technologies show promise in terms of improving clinical performance in the diagnosis and monitoring of mesothelioma patients. However, there is still no evidence that early detection can improve the treatment outcomes of PM patients.

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The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling

Cited by 4 publications

References 62 publications

Xanthohumol inhibits osteosarcoma proliferation, migration, and invasion via EFEMP1/PI3K/AKT axis

Xanthohumol inhibits osteosarcoma proliferation, migration, and invasion via EFEMP1/PI3K/AKT axis

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

Pleural Mesothelioma: Advances in Blood and Pleural Biomarkers

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