Recent Progress in HER2 Associated Breast Cancer

Wang, Weijia; Lei, Yuanyuan; Mei, Jin-Hong; Wang, Chunliang

doi:10.7314/apjcp.2015.16.7.2591

Cited by 23 publications

(15 citation statements)

References 93 publications

(158 reference statements)

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“…From the PLIN1 expression map of RSSPC classifications (Supplementary Figure 3E), we found the lowest levels of PLIN1 expression were exhibited in luminal B and basal-like subtype samples, which have a very low level of HER2 differs from the other three subtypes (Figure 5). Because HER2 plays an important role in the development and progression of breast cancer by mediating multiple signals in cancer cells [36], our findings suggest that HER2 status is involved in the downregulation of PLIN1 mRNA expression. Using the TCGA database, we also confirmed that reduced levels of PLIN1 expression correlate with significantly reduced overall survival rates.…”

Section: Discussionmentioning

confidence: 86%

Prognostic significance of PLIN1 expression in human breast cancer

et al. 2016

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Breast cancer is a heterogeneous disease associated with diverse clinical, biological and molecular features, presenting huge challenges for prognosis and treatment. Here we found that perilipin-1 (PLIN1) mRNA expression is significantly downregulated in human breast cancer. Kaplan-Meier analysis indicated that patients presenting with reduced PLIN1 expression exhibited poorer overall metastatic relapse-free survival (p = 0.03). Further Cox proportional hazard models analysis revealed that the reduced expression of PLIN1 is an independent predictor of overall survival in estrogen receptor positive (p < 0.0001, HR = 0.87, 95% CI = 0.81–0.92, N = 3,600) and luminal A-subtype (p = 0.02, HR = 0.88, 95% CI = 0.78–0.98, N = 1,469) breast cancer patients. We also demonstrated that the exogenous expression of PLIN1 in human breast cancer MCF-7 and MDA-MB-231 cells significantly inhibits cell proliferation, migration, invasion and in vivo tumorigenesis in mice. Together, these data provide novel insights into a prognostic significance of PLIN1 in human breast cancer and reveal a potentially new gene therapy target for breast cancer.

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Section: Discussionmentioning

confidence: 86%

Prognostic significance of PLIN1 expression in human breast cancer

et al. 2016

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“…Clearly, loss of PKD1 expression in context of PKD2/PKD3 expression drives oncogenic processes associated with metastatic progression [50, 78, 82]. This setting occurs in ER-negative IDC, which are the most aggressive breast cancers and associated with the worst outcome [83–86]. Preclinical studies using orthotopic animal models have shown that these invasive tumors which are characterized by the absence of PKD1 and high levels of PKD2/PKD3 can be targeted by two different strategies (Figure 5): 1) the re-activation of the epigenetically-silenced PRKD1 gene to block metastatic progression of highly invasive breast cancers; or 2) the chemical inhibition of the oncogenic PKD2/PKD3 to inhibit tumor growth, metastasis and chemoresistance [22, 23, 78].…”

Section: Protein Kinase D Enzymes As Therapeutic Targets For Advanmentioning

confidence: 99%

Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer

Durand

Borgés

Störz

2015

Cell. Mol. Life Sci.

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The Protein Kinase D (PKD) family members, PKD1, PKD2 and PKD3 constitute a family of serine/threonine kinases that are essential regulators of cell migration, proliferation and protein transport. Multiple types of cancers are characterized by aberrant expression of PKD isoforms. In breast cancer PKD isoforms exhibit distinct expression patterns and regulate various oncogenic processes. In highly-invasive breast cancer, the leading cause of cancer-associated deaths in females, the loss of PKD1 is thought to promote invasion and metastasis, while PKD2 and upregulated PKD3 have been shown to be positive regulators of proliferation, chemoresistance and metastasis. In this review, we examine the differential expression pattern, mechanisms of regulation and contributions made by each PKD isoform to the development and maintenance of invasive breast cancer. In addition, we discuss the potential therapeutic approaches for targeting PKD in this disease.

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“…However, these methods are limited to detect early genetic changes and predict the biologic behavior of the tumor. From the treatment standpoint, targeted cancer therapy is often dependent on overexpressed and activated oncogenes such as HER2/neu for breast cancer (31). However, in the majority of the solid tumors, tumor suppressor genes (TSG) act as the drivers of cancer development and progression (27).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Reprogramming Regulates Breast Cancer Progression

Kannan

Wells

Sivakumar³

et al. 2016

Clinical Cancer Research

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Purpose: The goal of this study was to understand the role of altered mitochondrial function in breast cancer progression and determine the potential of the molecular alteration signature in developing exosome-based biomarkers.Experimental Design: This study was designed to characterize the critical components regulating mitochondrial function in breast tumorigenesis. Experiments were conducted to assess the potential of these molecules for exosome-based biomarker development.Results: We observed a remarkable reduction in spontaneous metastases through the interplay in mitochondria by SH3GL2, vesicular endocytosis-associated protein and MFN2, an important regulator of mitochondrial fusion. Following its overexpression in breast cancer cells, SH3GL2 translocated to mitochondria and induced the production of superoxide and release of cytochrome C from mitochondria to the cytoplasm. These molecular changes were accompanied by decreased lung and liver metastases and primary tumor growth. SH3GL2 depletion reversed the above phenotypic and associated molecular changes in nontumorigenic and tumorigenic breast epithelial cells. Loss of SH3GL2 and MFN2 expression was evident in primary human breast cancer tissues and their positive lymph nodes, which was associated with disease progression. SH3GL2 and MFN2 expression was detected in sera exosomes of normal healthy women, but barely detectable in the majority of the women with breast cancer exhibiting SH3GL2 and MFN2 loss in their primary tumors.Conclusions: This study identified a new mitochondria reprogramming pathway influencing breast cancer progression through SH3GL2 and MFN2. These proteins were frequently lost in breast cancer, which was traceable in the circulating exosomes. Clin Cancer Res; 22(13); 3348-60. Ó2016 AACR.

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Recent Progress in HER2 Associated Breast Cancer

Cited by 23 publications

References 93 publications

Prognostic significance of PLIN1 expression in human breast cancer

Prognostic significance of PLIN1 expression in human breast cancer

Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer

Mitochondrial Reprogramming Regulates Breast Cancer Progression

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