PDF(Pubmed)
Abstract：
BACKGROUND: Triple negative breast cancer (TNBC) is a heterogeneous and aggressive disease characterized by a high risk of mortality and poor prognosis. It has been reported that Laminin γ2 (LAMC2) is highly expressed in a variety of tumors, and its high expression is correlated with cancer development and progression. However, the function and mechanism by which LAMC2 influences TNBC remain unclear.
METHODS: Kaplan-Meier survival analysis and Immunohistochemical (IHC) staining were used to examine the expression level of LAMC2 in TNBC. Subsequently, cell viability assay, wound healing and transwell assay were performed to detect the function of LAMC2 in cell proliferation and migration. A xenograft mouse model was used to assess tumorigenic function of LAMC2 in vivo. Luciferase reporter assay and western blot were performed to unravel the underlying mechanism.
RESULTS: In this study, we found that higher expression of LAMC2 significantly correlated with poor survival in the TNBC cohort. Functional characterization showed that LAMC2 promoted cell proliferation and migration capacity of TNBC cell lines via up-regulating CD44. Moreover, LAMC2 exerted oncogenic roles in TNBC through modulating the expression of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay verified that LAMC2 targeted ZEB1 to promote its transcription. Interestingly, LAMC2 regulated cell migration in TNBC via STAT3 signaling pathway.
CONCLUSIONS: LAMC2 targeted ZEB1 via activating CD44/STAT3 signaling pathway to promote TNBC proliferation and migration, suggesting that LAMC2 could be a potential therapeutic target in TNBC patients.
METHODS: Kaplan-Meier survival analysis and Immunohistochemical (IHC) staining were used to examine the expression level of LAMC2 in TNBC. Subsequently, cell viability assay, wound healing and transwell assay were performed to detect the function of LAMC2 in cell proliferation and migration. A xenograft mouse model was used to assess tumorigenic function of LAMC2 in vivo. Luciferase reporter assay and western blot were performed to unravel the underlying mechanism.
RESULTS: In this study, we found that higher expression of LAMC2 significantly correlated with poor survival in the TNBC cohort. Functional characterization showed that LAMC2 promoted cell proliferation and migration capacity of TNBC cell lines via up-regulating CD44. Moreover, LAMC2 exerted oncogenic roles in TNBC through modulating the expression of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay verified that LAMC2 targeted ZEB1 to promote its transcription. Interestingly, LAMC2 regulated cell migration in TNBC via STAT3 signaling pathway.
CONCLUSIONS: LAMC2 targeted ZEB1 via activating CD44/STAT3 signaling pathway to promote TNBC proliferation and migration, suggesting that LAMC2 could be a potential therapeutic target in TNBC patients.
摘要：
背景：三阴性乳腺癌（TNBC）是一种异质性和侵袭性疾病，其特征是死亡率高和预后差。据报道，层粘连蛋白γ2（LAMC2）在多种肿瘤中高表达，高表达与癌症的发生发展有关。然而,LAMC2影响TNBC的功能和机制尚不清楚.
方法：Kaplan-Meier生存分析和免疫组织化学（IHC）染色检测LAMC2在TNBC中的表达水平。随后，细胞活力测定，进行伤口愈合和transwell试验以检测LAMC2在细胞增殖和迁移中的功能。使用异种移植小鼠模型来评估体内LAMC2的致瘤功能。进行荧光素酶报告基因测定和蛋白质印迹以阐明潜在的机制。
结果：在这项研究中，我们发现,在TNBC队列中,LAMC2的高表达与低生存率显著相关.功能表征显示LAMC2通过上调CD44促进TNBC细胞系的细胞增殖和迁移能力。此外，LAMC2通过调节上皮-间质转化（EMT）标志物的表达在TNBC中发挥致癌作用。荧光素酶报告基因测定证实LAMC2靶向ZEB1以促进其转录。有趣的是,LAMC2通过STAT3信号通路调节TNBC细胞迁移。
结论：LAMC2通过激活CD44/STAT3信号通路靶向ZEB1促进TNBC增殖和迁移，提示LAMC2可能是TNBC患者的潜在治疗靶点。
方法：Kaplan-Meier生存分析和免疫组织化学（IHC）染色检测LAMC2在TNBC中的表达水平。随后，细胞活力测定，进行伤口愈合和transwell试验以检测LAMC2在细胞增殖和迁移中的功能。使用异种移植小鼠模型来评估体内LAMC2的致瘤功能。进行荧光素酶报告基因测定和蛋白质印迹以阐明潜在的机制。
结果：在这项研究中，我们发现,在TNBC队列中,LAMC2的高表达与低生存率显著相关.功能表征显示LAMC2通过上调CD44促进TNBC细胞系的细胞增殖和迁移能力。此外，LAMC2通过调节上皮-间质转化（EMT）标志物的表达在TNBC中发挥致癌作用。荧光素酶报告基因测定证实LAMC2靶向ZEB1以促进其转录。有趣的是,LAMC2通过STAT3信号通路调节TNBC细胞迁移。
结论：LAMC2通过激活CD44/STAT3信号通路靶向ZEB1促进TNBC增殖和迁移，提示LAMC2可能是TNBC患者的潜在治疗靶点。
