&lt;p&gt;Hepsin Promotes Epithelial–Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer&lt;/p&gt;

Li, Ruiqian; Li, Jun; Yang, Hong; Bai, Yu; Hu, Chen; Wu, Hongyi; Jiang, Haiyang; Wang, Qilin

doi:10.2147/ott.s268025

Cited by 10 publications

(9 citation statements)

References 43 publications

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“…Although HPN is part of this proteolytic complex, contributing to a degradation of the pericellular microenvironment, its net effect on tumorigenesis is complex and context dependent. Thus, in prostate cancer, HPN has a clear pro-tumorigenic function by promoting invasion processes in certain settings [9]. However, other reports in the literature suggest that very high levels of this serine protease may exert paradoxical antitumor effects with limitation of oncogenic signaling and increased autophagy [10].…”

Section: Introductionmentioning

confidence: 99%

Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients

Zaragoza-Huesca

Nieto-Olivares

García‐Molina

et al. 2022

Cancers

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Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal–Wallis tests, Kaplan–Meier and Aalen–Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.

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Section: Introductionmentioning

confidence: 99%

Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients

Zaragoza-Huesca

Nieto-Olivares

García‐Molina

et al. 2022

Cancers

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“…Although HPN is part of this proteolytic complex, contributing to degrade the pericellular microenvironment, its net effect on tumorigenesis is complex and context-dependent. Thus, in prostate cancer, HPN has a clear pro-tumorigenic function by promoting invasion processes in certain settings (9). However, other reports in the literature suggest that very high levels of this serine protease may exert paradoxical antitumor effects with limitation of oncogenic signaling and increased autophagy (10).…”

Section: Introductionmentioning

confidence: 99%

Implication of Hepsin from primary tumor in the prognosis of colorectal cancer patients

Zaragoza-Huesca

Nieto-Olivares

García‐Molina

et al. 2022

Preprint

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BackgroundHepsin is a type II transmembrane serine protease whose functions include degradation of the extracellular matrix and activation of factor VII. In many tumors, hepsin dysregulation leads to tumor invasion by proteolysis of pericellular components. Colorectal cancer is a tumor with high thrombotic and metastatic risk, but the role of hepsin is unknown.ObjectivesTo study the correlations between hepsin expression in the primary tumor and different clinical-histopathological variables in patients with localized and metastatic colorectal cancer.MethodsA cohort of 287 patients, 169 with localized colorectal cancer and 118 with metastases at diagnosis, was recruited. Tissue microarrays were made from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin levels were determined and the association with clinical-histopathological variables was evaluated using the chi-square and Kruskal-Wallis tests. Time-to-event results and cumulative incidence functions were calculated using Kaplan-Meier and Aalen-Johansen estimators, in combination with Cox and Fine&Gray multivariate models.ResultsIn patients with localized colorectal cancer, high intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). In this context, according to multivariable Cox regression, medium and high intensity of hepsin expression versus low intensity was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value=0.035, and hazard ratio 3.30, p-value=0.012, respectively), being a more accurate prognostic factor than classic histological variables. Also, in patients with localized colorectal cancer, the cumulative incidence of thrombosis at 5 years increased significantly with higher hepsin levels (p-value = 0.038). According to the multivariate Fine&Gray regression, the medium and high intensity of hepsin with respect to the low intensity, was associated with an increase in thrombotic risk (hazard ratio 7.71, p-value=0.043 and hazard ratio 9.02, p-value=0.028, respectively). This relationship between hepsin and thrombosis was independent of previous tumor relapse (p-value = 0.036). In patients with metastatic colorectal cancer, low intensity of hepsin was associated with a low degree of tumor differentiation (p-value <0.001) and spread to more than one metastatic site (p-value = 0.023).ConclusionHepsin is a potential biomarker of thrombosis and metastasis in patients with localized colorectal cancer. Validation in a larger series and clarification of the underlying mechanism may be helpful in evaluating these patients. In metastatic patients, Hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.

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“…PPP2R2A is considered as a tumor suppressor in human cancers. 35 , 36 Yu et al reported that overexpression of miR-221 could promote osteosarcoma cell proliferation and cisplatin resistance via downregulation of PPP2R2A. 37 Zhang et al found that miR-136 could promote the proliferation of vascular muscle cells in atherosclerosis via targeting PPP2R2A.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A

Gu¹,

Hu²,

Hui³

et al. 2021

IJN

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Background: Anlotinib resistance is a challenge for advanced non-small cell lung cancer (NSCLC). Understanding the underlying mechanisms against anlotinib resistance is of great importance to improve prognosis and treatment of patients with advanced NSCLC. Methods: RT-qPCR assay was used to assess the level of miR-136-5p in anlotinib-resistant NSCLC cells and exosomes derived from anlotinib-resistant NSCLC cells. In addition, miR-136-5p level in tumor tissues from patients who exhibited a poor response to anlotinib therapy and patients who were therapy naïve or patients who exhibited a positive response to anlotinib therapy was detected by RT-qPCR assay. Results: In this study, we found that high levels of plasma exosomal miR-136-5p is correlated with clinically poor anlotinib response. In addition, anlotinib-resistant NSCLC cells promoted parental NSCLC cell proliferation via transferring functional miR-136-5p from anlotinib-resistant NSCLC cells to parental NSCLC cells via exosomes. Moreover, exosomal miR-136-5p could endow NSCLC cells with anlotinib resistance by targeting PPP2R2A, leading to the activation of Akt pathway. Furthermore, miR-136-5p antagomir packaging into anlotinib-resistant NSCLC cell-derived exosomes functionally restored NSCLC cell anlotinib sensitivity in vitro. Animal studies showed that A549/anlotinib cellderived exosomal miR-136-5p agomir promoted A549 cell anlotinib resistance in vivo. Conclusion: Collectively, these findings indicated that anlotinib-resistant NSCLC cellderived exosomal miR-136-5p confers anlotinib resistance in NSCLC cells by targeting PPP2R2A, indicating miR-136-5p may act as a potential biomarker for anlotinib response in NSCLC.

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<p>Hepsin Promotes Epithelial–Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer</p>

Cited by 10 publications

References 43 publications

Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients

Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients

Implication of Hepsin from primary tumor in the prognosis of colorectal cancer patients

Exosomal miR-136-5p Derived from Anlotinib-Resistant NSCLC Cells Confers Anlotinib Resistance in Non-Small Cell Lung Cancer Through Targeting PPP2R2A

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