scholarly journals Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xiu-Feng Wang ◽  
Jia Du ◽  
Tian-Ling Zhang ◽  
Qian-Mei Zhou ◽  
Yi-Yu Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Metastasis ◽  
Proteolytic Enzymes ◽  
Breast Cancer Metastasis ◽  
Herbal Extract ◽  
Dependent Manner ◽  
Matrix Degradation ◽  
Human Breast

Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell linein vivoandin vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasionin vitroin a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.

scholarly journals Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yingqi Liu ◽  
Lingling Li ◽  
Xiaoqing Liu ◽  
Yibo Wang ◽  
Lingxia Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Metastasis ◽  
Arginine Methylation ◽  
Breast Cancer Metastasis ◽  
Human Breast ◽  
Clinical Breast ◽  
Cancer Tissues

Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal FAK/cortactin signals in vitro and in vivo. Consistently, all the levels of PRMT7, methylated SHANK2, FAK Y397 phosphorylation and cortactin Y421 phosphorylation were correlated with aggressive clinical breast cancer tissues. These findings characterize the PRMT7-dependent SHANK2 methylation as a key player in mediating endosomal FAK signals activation, also point to the value of SHANK2 R240 methylation as a target for breast cancer metastasis.

A novel and selective inhibitor of PKC ζ potently inhibits human breast cancer metastasis in vitro and in mice

Tumor Biology ◽  
2016 ◽  
Vol 37 (6) ◽  
pp. 8391-8401 ◽  
Author(s):  
Jing Wu ◽  
Shuye Liu ◽  
Zhijuan Fan ◽  
Lei Zhang ◽  
Yaqiong Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Selective Inhibitor ◽  
Human Breast ◽  
Pkc Ζ

scholarly journals A New Mouse Model for the Study of Human Breast Cancer Metastasis

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47995 ◽  
Author(s):  
Elizabeth Iorns ◽  
Katherine Drews-Elger ◽  
Toby M. Ward ◽  
Sonja Dean ◽  
Jennifer Clarke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Human Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Human Breast

scholarly journals KIF21A influences breast cancer metastasis and survival

2016 ◽  
Author(s):  
Anton J. Lucanus ◽  
Victoria King ◽  
George W. Yip
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Tissue ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Human Breast ◽  
Mcf 7

ABSTRACTBreast cancer pathogenesis is known to be propagated by the differential expression of a group of proteins called the Kinesin Superfamily (KIFs), which are instrumental in the intracellular transport of chromosomes along microtubules during mitosis. During mitosis, KIFs are strictly regulated through temporal synthesis so that they are only present when needed. However, their misregulation may contribute to uncontrolled cell growth due to premature sister chromatid separation, highlighting their involvement in tumorigenesis. One particular KIF, KIF21A, was recently found to promote the survival of human breast cancer cells in vitro. However, how KIF21A influences other cancerous phenotypes is currently unknown. This study therefore aimed to consolidate the in vitro role of KIF21A in breast cancer metastasis, while also analysing KIF21A expression in human breast cancer tissue to determine its prognostic value. This was achieved by silencing KIF21A in MCF-7 and MDA-MB-231 breast cancer cell lines via siRNA transfection. Migration, invasion, proliferation, and adhesion assays were then performed to measure the effects of KIF21A silencing on oncogenic behaviour. Immunohistochemistry was also conducted in 263 breast cancer tissue samples to compare KIF21A expression levels against various prognostic outcomes and clinicopathological parameters. KIF21A knockdown reduced cell migration (by 42.8% [MCF-7] and 69.7% [MDA-MB-231]) and invasion (by 72.5% [MCF-7] and 42.5% [MDA-MB-231]) in both cell lines, but had no effect on adhesion or proliferation, suggesting that KIF21A plays an important role in the early stages of breast cancer metastasis. Unexpectedly however, KIF21A was shown to negatively correlate with various pro-malignant clinicopathological parameters, including tumour size and histological grade, and high KIF21A expression predicted better breast cancer survival (hazard ratio = 0.45), suggesting that KIF21A is a tumour suppressor. The conflicting outcomes of in vitro and in vivo data may be due to the possible multi-functionality of KIF21A or study limitations, and means no definitive conclusions can be drawn about the role of KIF21A in breast cancer. This warrants further investigation, which may prove pivotal to the development of novel chemotherapeutic strategies to mediate KIF21A’s function and enhance prognostic outcomes.

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