Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognosis of invasive breast cancer

Cao²,

et al. 2010

Cancer Science

Self Cite

Protein interacting with C a kinase 1 (PICK1), which interacts with multiple different proteins in a variety of cellular contexts, is believed to play important roles in diverse pathological conditions including cancer. In this study, we attempted to investigate the correlation of PICK1 with clinicopathological features as well as prognosis of human breast cancer. In addition, we aimed at a better understanding of the biological function of PICK1 in breast cancer cell biology. As judged by semi-quantitative RT-PCR and western blotting, PICK1 was overexpressed in tumor cells as compared to adjacent normal epithelia in breast, lung, gastric, colorectal, and ovarian cancer. As judged by immunostaining breast cancer tissue microarrays, high levels of PICK1 expression correlated with shortened span of overall survival (OS). Protein interacting with C a kinase 1 (PICK1) expression seemed to be specifically associated with reduced OS in lymph node-positive, Her ⁄ neu-2 positive, and the basal-like type subgroups, respectively. Consistently, the expression of PICK1 correlated with histological grade, lymph node metastasis, Her-2 ⁄ neu-positivity, and triple-negative basal-like breast cancer. Protein interacting with C a kinase 1 (PICK1) was not correlated with menopausal status, tumor size, or hormone receptor status. In a complementary study, transfection of MDA-MB-231 cells with PICK1 siRNA decreased cell proliferation and colony formation in vitro and inhibited tumorigenicity in nude mice. Our clinical and experimental evidence supports an oncogenic role of PICK1 in human breast cancer. In particular, our data suggest that PICK1 promotes tumor cell proliferation. Taken together, PICK1 may serve not only as a marker for poor prognosis, but also as a therapeutic target in breast cancer. (Cancer Sci 2010; 101: 1536-1542 B reast cancer is one of the leading causes of cancer death among women worldwide.(1) The incidence and mortality rate of breast cancer have increased sharply in China over the past few decades, (2) whereas the breast cancer mortality rate in developed countries has declined in the same period, likely due to the implementation of screening, (3) improvements in early breast cancer management, (4) and improved systemic adjuvant treatments.(5) Currently, the strategy for breast cancer management is primarily based on the traditional prognostic and predictive factors including histologic, clinical, and some well-defined molecular profiles. Since the biomarker profile may provide valuable insights into the underlying mechanisms of disease progression, (6,7) in light of the well-documented racial disparities in breast cancer incidence and prognosis, it is important to identify and validate specific biomarkers for Chinese breast cancer patients.Protein interacting with C a kinase 1 (PICK1), a PSD95 ⁄ disklarge ⁄ ZO-1 (PDZ) domain-containing protein, was originally identified by a yeast two-hybrid system on the basis of its interaction with protein kinase C a (PKCa). (8,9) In addition to PKCa,PICK1 also interac...

Section: Immunohistochemical (Ihc) Quantificationmentioning

confidence: 99%

Section: Immunohistochemical (Ihc) Quantificationmentioning

confidence: 99%

Section: Tissue Microarrays (Tma) and Immunohistochemistry (Ihc)mentioning

confidence: 99%

See 1 more Smart Citation

Protein interacting with C α kinase 1 (PICK1) is involved in promoting tumor growth and correlates with poor prognosis of human breast cancer

Cao²,

et al. 2010

Cancer Science

Self Cite

“…TMAs were constructed using a Beecher Instruments Tissue Array (Beecher Instruments, Silver Spring, MD, USA) (16). Briefly, archival paraffin blocks containing invasive ductal carcinoma tissues were selected.…”

Section: Introductionmentioning

confidence: 99%

PAX6 overexpression is associated with the poor prognosis of invasive ductal breast cancer

et al. 2015

Abstract. Paired box 6 (PAX6) plays a significant role in the development of human neuroectodermal epithelial tissues. Previous studies have suggested that the PAX6 promoter is hypermethylated in breast cancer and that it is involved in breast cancer cell proliferation. The present study aimed to investigate the expression of PAX6 in invasive breast cancer tissues, and to evaluate its prognostic significance. Immunohistochemistry (IHC) was used to detect PAX6 expression on a breast cancer tissue microarray containing tissues from 111 patients. Associations of PAX6 expression with staging and prognosis were analyzed. PAX6 was mainly expressed in the nucleus. The PAX6 staining intensity was not associated with age, histological grade, lymph node status, tumor size, or progesterone receptor and human epidermal growth factor receptor 2 expression (all P>0.05). A high level of PAX6 staining was more frequent in estrogen receptor (ER)-negative cases compared with ER-positive cases (43.9 vs. 25.7%; P= 0.049). After a median follow-up time of 110 months, the patients with low PAX6 expression exhibited an improved survival rate compared with the patients with high PAX6 expression (P<0.001). Cox analysis showed a worse survival rate in the patients with high PAX6 staining (hazard ratio, 3.458; 95% confidence interval, 1.575-7.593; P= 0.002). In conclusion, high tumor PAX6 staining intensity by IHC was associated with a poor prognosis in breast cancer patients.

American Journal of Physiology-Cell Physiology

“…In other cell types, MMP-13 activity is central to cell migration, most evident in breast carcinoma metastasis (32). In addition, it plays an important role in cutaneous wound healing (31) and bone formation (14).…”

mentioning

confidence: 99%

Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration

Lei

Leong

Smith

et al. 2013

Lei H, Leong D, Smith LR, Barton ER. Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration. Am J Physiol Cell Physiol 305: C529-C538, 2013. First published June 12, 2013 doi:10.1152/ajpcell.00051.2013.-Efficient skeletal muscle repair and regeneration require coordinated remodeling of the extracellular matrix (ECM). Previous reports have indicated that matrix metalloproteinases (MMPs) play the pivotal role in ECM remodeling during muscle regeneration. The goal of the current study was to determine if the interstitial collagenase MMP-13 was involved in the muscle repair process. Using intramuscular cardiotoxin injections to induce acute muscle injury, we found that MMP-13 expression and activity transiently increased during the regeneration process. In addition, in muscles from mdx mice, which exhibit chronic injury, MMP-13 expression and protein levels were elevated. In differentiating C2C12 cells, a murine myoblast cell line, Mmp13 expression was most pronounced after myoblast fusion and during myotube formation. Using pharmacological inhibition of MMP-13 to test whether MMP-13 activity is necessary for the proliferation, differentiation, migration, and fusion of C2C12 cells, we found a dramatic blockade of myoblast migration, as well as a delay in differentiation. In contrast, C2C12 cells with stable overexpression of MMP-13 showed enhanced migration, without affecting myoblast maturation. Taken together, these results support a primary role for MMP-13 in myoblast migration that leads to secondary effects on differentiation.collagenase; matrix metalloproteinase; muscle repair; myoblast maturation