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Osteosarcoma is the most common primary malignant bone tumor, which occurs in adolescents. As reported by our previous studies, HER4 indicates a poor prognosis of primary osteosarcoma. However, its mechanisms in the pathogenesis of osteosarcoma have not yet been studied. The purpose of this study was to investigate the role of HER4 in osteosarcoma and whether the PI3K/AKT pathway is involved. In this study, western blot analysis was used to investigate the expression of HER4 protein in osteosarcoma tissues and cell lines. CCK8 and transwell assays were used to detect the effects of HER4 on the proliferation, migration, and invasion of osteosarcoma cells in vitro. The effects of HER4 on the growth and metastasis of osteosarcoma in vivo were detected by tumor formation and immunofluorescence in nude mice. The role of the PI3K/AKT pathway in HER4 regulation of the growth and metastasis of osteosarcoma was examined by western blot analysis and immunofluorescence assay. We found that HER4 protein was highly expressed in clinical osteosarcoma specimens and osteosarcoma cells. HER4 markedly promoted the proliferation, migration, and invasion of osteosarcoma cells in vitro as well as the growth and metastasis of osteosarcoma in vivo. HER4 overexpression upregulated the expression of phosphorylated protein kinase B (pAKT), proliferation marker antigen Ki67, and metastasis cell marker matrix metalloproteinase 9 (MMP9). Notably, PI3K/AKT inhibitor LY294002 significantly inhibited the effects of HER4 via the downregulation of pAKT, Ki67, and MMP9. Moreover, LY294002 markedly blocked the effects of HER4-induced upregulation of tumor malignancy. The present study suggests that HER4 may promote the growth and metastasis of osteosarcoma via the PI3K/AKT pathway. The HER4/PI3K/AKT pathway could serve as a potential target for the treatment of osteosarcoma.

Alpha-actinin-4 (ACTN4) is associated with different types of tumors, but its role in osteosarcoma (OS) is not known. We aimed to investigate the effect of ACTN4 on the growth, migration, invasion and metastasis of OS. We further explored the possible mechanism of how ACTN4 affects the development of OS. First, the expression of ACTN4 in OS tissues and OS cell lines was analyzed by PCR. Second, the role of ACTN4 in the development of OS was explored by the proliferation, scratch, and invasion assays. We further explored the effect of ACTN4 on OS growth in an orthotopic xenograft model of nude mice. In addition, we used hematoxylin and eosin (HE) staining of lung tissues in nude mice to observe the effect of ACTN4 on lung metastasis of OS. Finally, rescue experiments further investigated the role of NF-κB on ACTN4 in the development of OS. ACTN4 was highly expressed in OS tissues and OS cell lines. In vitro experiments demonstrated that reducing ACTN4 expression inhibited the proliferation, migration, and invasion of OS. In contrast, overexpression of ACTN4 promotes these effects. In vivo experiments further validated that ACTN4 promoted the growth of OS. The HE staining of lungs in nude mice revealed that ACTN4 promoted lung metastasis of OS. In addition, we found that ACTN4 enhanced the ability of OS to invade, through the NF-κB pathway. ACTN4 promotes the proliferation, migration, metastasis of OS and enhances its invasion ability through the NF-κB pathway.

Fengqiang Yu,* Weihan Wu,* Mingqiang Liang,* Yu Huang, Chun Chen Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun ChenDepartment of Thoracic Surgery, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaTel +86 13365910325Fax +86 591-83357896-8408Email chenchun0209@163.comPurpose: Rab27A and Rab27B, members of the Rab family of small GTPases, have aberrant expression and exert different roles in various cancers. However, their expression and potential prognostic values in esophageal squamous cell cancer (ESCC) still remain elusive. In the present study, we explored the association of Rab27A and Rab27B expression with clinical significance and prognosis in ESCC.Patients and Methods: A total of 100 surgically resected ESCC tissues were examined to evaluate Rab27A and Rab27B expression levels using the immunohistochemistry method. The relationship of Rab27A and Rab27B with clinicopathological features and prognosis was analyzed. We also investigated the correlation between Rab27A and Rab27B through external and internal validation.Results: High-expression Rab27A was found to be significantly correlated with N (p=0.045) and TNM (p=0.005) stage, while up-regulated Rab27B was remarkably associated with N stage (p=0.033), TNM stage (p=0.009), and differentiation (p=0.013). High expression of both Rab27A and Rab27B had a worse overall survival (OS) rate. In addition, multivariate Cox regression analyses were utilized to validate that Rab27B expression is an independent prognostic factor for unfavorable OS. Further combined analyses showed that the Rab27Alow/Blow group had a superior OS rate than the Rab27Ahigh/Blow group, Rab27Alow/Bhigh group, and Rab27Ahigh/Bhigh group. Nevertheless, the latter three groups displayed rare significance between each two comparisons. Furthermore, our data demonstrated that Rab27A expression was positively correlated with Rab27B expression, which were also verified in TCGA datasets.Conclusion: Rab27A and Rab27B expression levels could be potentially novel prognostic biomarkers in ESCC.Keywords: Rab27A, Rab27B, esophageal squamous cell cancer, prognosis, survival analysis

Background Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvβ3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvβ3 in osteosarcoma. Methods Immunohistochemistry and western blotting were used to detect the expression of FN and αvβ3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and αvβ3 with the clinicopathological features of osteosarcoma patients were analyzed using the χ2 test and Fisher’s exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index. Results FN (P