ABSTRACT
OBJECTIVE: To investigate role and clinical significance of CDK13 in breast cancer patients. METHODS: A total of 189 cases of breast cancer were enrolled during March 2013 to March 2015. Immunohistochemistry (IHC) was used for measurement of CDK13, HIF-1α and beclin1. Clinical characteristics of age, BMI, TNM stage, pathological types, and tumor diameter, were recorded. Patients' 5-year overall survival and recurrence were followed up. All patients were followed up for 5 years or to the last follow-up. RESULTS: The expression levels of CDK13 and HIF-1αin breast cancer tissues were up-regulated and beclin1 was down-regulated than in the paracancerous non-tumor tissues. CDK13 was positively correlated with HIF-1α and negatively correlated with beclin1 in breast cancer tissues. The patients with higher expression of CDK13 showed significantly higher rates of TNM III-IV, higher rates of lymph node metastasis, distant metastasis and larger tumor size. The mortality and recurrence rates were higher in high expression CDK13 patients than in low CDK13 expression patients, however with no significant difference. K-M curve showed patients with higher CDK13 showed lower 5-year overall survival and lower disease-free survival time, however with no significant difference. CONCLUSION: CDK13 was overexpressed in breast cancer tissues, and patients with higher CDK13 had poorer clinical outcomes. Further studies are still needed to reveal the clinical significance of CDK13 in breast cancer.
Subject(s)
Beclin-1 , Breast Neoplasms , CDC2 Protein Kinase/genetics , Hypoxia-Inducible Factor 1, alpha Subunit , Beclin-1/genetics , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Disease-Free Survival , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lymphatic Metastasis , PrognosisSubject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , p21-Activated Kinases/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Animals , Apoptosis/drug effects , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Proliferation/drug effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Heterografts , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Mice , Middle AgedABSTRACT
p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.
ABSTRACT
BACKGROUND: Tartrate-resistant acid phosphatase 5 (ACP5) is an evolutionarily conserved and multifunctional protein that is involved in generations of reactive oxygen species, normal bone development, osteoblast regulation and macrophage function, affecting a series of pathways, as well as reflecting bone resorption and osteoclast activity. METHODS: Literature searches, systematic reviews and assessments about the structure, distribution, regulation and novel functions of ACP5 were performed in this review from PubMed and Medline databases. RESULTS: Studies demonstrate that RANKL can increase the expression of ACP5 through NFATc1 and c-Fos to accelerate osteoclastogenesis, which also can be regulated by many regulators. Based on the aforementioned information, it is shown that ACP5, together with the phosphatase activity, can medicate the progression and development of human genetic diseases and cancer. CONCLUSION: As a novel target, ACP5 plays a critical role in preventing, monitoring and treating various kinds of tumors, as well as accelerating the development of a promising therapeutic strategy for human genetic diseases. However, the explicit mechanism between ACP5 and cancer is not so clear. It is necessary and significant for us to pay more in-depth attention.
Subject(s)
Neoplasms/metabolism , Tartrate-Resistant Acid Phosphatase/metabolism , Humans , Protein Conformation , Tartrate-Resistant Acid Phosphatase/chemistryABSTRACT
High-mobility group protein box 1(HMGB1)is a ubiquitous highly conserved nuclear protein. Acting as a chromatin-binding factor, HMGB1 binds to DNA and plays an important role in stabilizing nucleosome formation, facilitating gene transcription, DNA repairing, inflammation, cell differentiation, and regulating the activity of steroid hormone receptors. Currently, HMGB1 is discovered to be related to development, progression, and targeted therapy of lung cancer, which makes it an attractive biomarker, and therapeutic target. This review aims to encapsulate the relationship between HMGB1 and lung cancer, suggesting that HMGB1 plays a pivotal role in initiation, development, invasion, metastasis, and prognosis of lung cancer.
Subject(s)
Biomarkers, Tumor/metabolism , HMGB1 Protein/metabolism , Lung Neoplasms/metabolism , Neoplasm Proteins/metabolism , Animals , Biomarkers, Tumor/genetics , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , HMGB1 Protein/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/genetics , Nucleosomes/genetics , Nucleosomes/metabolism , Nucleosomes/pathologyABSTRACT
BACKGROUND: Abnormal proliferation is significantly associated with the promotion of malignant tumor. Growing evidence suggest that the signal pathways of p21cdc42/rac1-activated kinase 5 (PAK5) have been found in various tumor progression, however, the role of PAK5 in breast cancer remains largely unclear. METHODS: We evaluated PAK5 and p65 staining in breast cancer tissues (BCTs) and paired non-cancerous tissues (NTs) using tissue microarray (TMA) technology. The functions of PAK5 were studied in vitro and in vivo. Cell Counting Kit-8 (CCK-8) and flow cytometry were performed to determine proliferation of breast cancer cells. Phosphorylation assay and co-immunoprecipitation (co-IP) were employed to identify the regulation mechanism of p65 by PAK5. The activation of Cyclin D1 promoter was measured with luciferase reporter assay. Xenograft models in nude mice were established to explore the roles of PAK5 in breast cancer growth. RESULTS: In this study, we show that PAK5 is highly expressed in breast cancer tissues and the increased PAK5 is significantly associated with breast cancer progression. Overexpression of PAK5 promotes the proliferation and cell-cycle progression by increasing the expression of Cyclin D1 in vitro and in vivo. Mechanistic studies demonstrated that PAK5 can promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB (NF-κB). Furthermore, p65 can directly bind to the promoter of Cyclin D1 and mediate an increase in its protein expression. CONCLUSIONS: Taken together, our findings suggest that PAK5 may serve as a potential prognosis marker and therapeutic target for human breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Transcription Factor RelA/metabolism , p21-Activated Kinases/metabolism , Animals , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cyclin D1/metabolism , Disease Models, Animal , Female , Follow-Up Studies , Gene Expression , Genes, Reporter , Heterografts , Humans , Immunohistochemistry , Mice , Neoplasm Staging , Phosphorylation , Prognosis , Promoter Regions, Genetic , Protein Transport , Signal Transduction , Transcriptional Activation , Tumor Burden , p21-Activated Kinases/geneticsABSTRACT
Egr-1 is an important nuclear transcription factor in the early growth response gene family (Egr family). Egr-1 was reportedly involved in the tumorigenesis of diverse tumors. However, there was a paucity of data regarding the role of Egr-1 in the breast cancer. Herein, we investigated the expression of Egr-1 in breast tissues and breast cancer cell lines BT549 and Bcap37. Immunohistochemistry showed that Egr-1 was down-regulated in breast cancer tissues versus the normal paracancerous tissues. Overexpression of Egr-1 could arrest the progression of cell cycle in breast cancer cells. Luciferase reporter assay revealed Egr-1 could bind to the promoters of CyclinD1, CyclinD2 and CyclinD3. Together, these results suggested that Egr-1 could affect the cell cycle of breast cancer cells and defined the mechanism for the cells by inhibiting the process of G0/G1 phase. Our findings provide new insight into Egr-1 in breast cancer.
