Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is now a considerable body of evidence that links HPV infection with anogenital squamous carcinoma, particularly for specific 'high risk' HPV types (HPV16 and 18) and invasive carcinoma of the cervix. Recent advances in the molecular study of these viruses have elucidated some potential mechanisms by which they may contribute to the development of these diseases. In this review we concentrate on the interactions of 2 of the HPV encoded proteins, E6 and E7, with cellular tumour suppressor gene products. We provide a model of how these interactions may be important in tumourigenesis and draw together current knowledge of this exciting and rapidly evolving field.
Int J STD AIDS
PMID:Human papillomaviruses, tumour suppressor genes and cervical cancer. 839 53

Several lines of evidence have demonstrated that IFNs could be relevant in the treatment of certain neoplastic diseases such as carcinomas. In particular, IFN-alpha, in addition to the anti-proliferative and cytostatic effects, was demonstrated to be capable of inducing cell death by apoptosis both in vivo and in vitro. Numerous protocols have also been proposed which consider the association of IFN-alpha with other drugs. Among these are retinoids, a class of compounds capable of inducing inhibition of cell growth and differentiation. We address the question here by analyzing the role of cell adhesion in susceptibility to IFN-alpha, RA and their combination of a human cell line derived from a squamous carcinoma of the cervix, the Bcl-2-negative SiHa cell line. In this context, cytoskeleton components and several surface molecules playing a role in cell substrate and cell-to-cell relationships have been evaluated. We found that RA treatment is capable of improving stress fiber formation, decreasing cell detachment and increasing cell-adhesion capability. However, no variations in the ability to adhere to specific extracellular-matrix molecules were found in RA-treated cells. No quantitative changes were detected in integrins involved as receptors for extracellular matrix molecules (VLAI-VLA5) or in other cell-adhesion-associated molecules (e.g., CD44). By contrast, 2 important molecules involved in cell-adhesion processes appeared to be up-regulated by RA exposure: focal adhesion kinase and E-cadherin, involved in adhesion plaque formation and cell-to-cell contacts, respectively. Keeping in mind the importance of adhesion properties in the cell-growth pathway, our findings could be of interest in the study of carcinoma-cell proliferation and metastatic potential.
 ...
PMID:Antiproliferative activity of interferon alpha and retinoic acid in SiHa carcinoma cells: the role of cell adhesion. 959 Jan 30

Cancer antigens RAK-p120, p42, and p25, which exhibit biological, immunological and molecular similarity to the proteins expressed by Human Immunodeficiency Virus 1 (HIV-1), were found in 47 of 47 tested cases of serous adenocarcinoma of the ovary, and 45 of 45 tested cases of squamous carcinoma of the cervix. Normal ovary and cervix did not express antigens RAK. High molecular weight protein (RAK-p160) was detected in the blood of over 61% of ovarian and 72% of cervical cancer patients, and in 14.3% of healthy women with family history of breast and/or gynecological cancer. Antigens RAK might represent new diagnostic markers.
 ...
PMID:Diagnostic evaluation of cancer antigens RAK .1. Cervical and ovarian cancer. 2154 70

Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.
 ...
PMID:Tetraspanin 1 promotes invasiveness of cervical cancer cells. 2375 16

Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts. Gene set enrichment analysis (GSEA) showed that metastasis, cell cycle and FAK pathways were related with elevated CKAP2 expression. Knockdown of CKAP2 expression significantly inhibited cell proliferation, migration and invasion both in HeLa and C-33A cells. And depletion of CKAP2 down-regulated the expression of metastasis and cell cycle related proteins as well as the phosphorylation of ERK2 (p-ERK2), except E-cadherin. In vivo experiment revealed that knockdown of CKAP2 inhibited C-33A cells proliferation. However, FAK inhibitor PF-562271 and ERK2 inhibitor VX-11e treatment significantly inhibited CKAP2 overexpression-induced cell proliferation, migration and invasion in SiHa cells. In conclusion, our study suggests that CKAP2 acts as a functional oncogene in cervical carcinoma development and may exert its function by targeting FAK-ERK2 signaling pathway.
 ...
PMID:Involvement of FAK-ERK2 signaling pathway in CKAP2-induced proliferation and motility in cervical carcinoma cell lines. 2852 60

Cervical carcinoma remains the second most common malignancy with a high mortality rate among women worldwide. TAD-1822-7-F2 (F2) and TAD-1822-7-F5 (F5) are novel compounds synthesized on the chemical structure of taspine derivatives, and show an effective suppression for HeLa cells. Our study aims to confirm the potential targets of F2 and F5, and investigate the underlying mechanism of the inhibitory effect on HeLa cells. In this study, Real Time Cell Analysis and crystal violet staining assay were conducted to investigate the effect of F2 and F5 on HeLa cells proliferation. And the analytical methods of surface plasmon resonance and quartz crystal microbalance were established and employed to study the interaction between F2 and F5 and potential target protein JAK2, suggesting that both compounds have strong interaction with the JAK2 protein. Western blot analysis, immunofluorescence staining study and PCR was conducted to investigate the molecules of JAK/Stat signaling pathway. Interestingly, F2 and F5 showed diverse regulation for signaling molecules because of their different chemical structure. F2 increased the expression of JAK2 and downregulated the level of P-JAK1 and P-JAK2, and decreased P-Stat3 (Ser727). While F5 could increase the expression of JAK2 and naturally decrease the phosphorylation of JAK1 and Tyk2, and decreased the expression of P-Stat6. Moreover, F2 and F5 showed the same downregulation on the P-Stat3 (Tyr705). Therefore, F2 and F5 could target the JAK2 protein and prevent the phosphorylation of JAKs to suppress the phosphorylation of the downstream effector Stats, which suggested that F2 and F5 have great potential to be the inhibitors of the JAK/Stat signaling pathway.
 ...
PMID:Novel compounds TAD-1822-7-F2 and F5 inhibited HeLa cells growth through the JAK/Stat signaling pathway. 2964 26

Cervical carcinoma is one of the most universal cancers among women. Recent researches have reported that microRNA-150-5p (miR-150-5p) is up-regulated in diverse carcinomas containing cervical carcinoma. The purpose of this study was to further investigate the potential role of miR-150-5p in the progress of cervical carcinoma cells including proliferation and epithelial-mesenchymal transition (EMT).The ability of miR-150-5p to promote carcinogenesis was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot assays, respectively. Bioinformatics analyses predicted and identified whether SRC kinase signaling inhibitor 1 (SRCIN1) was served as a potential target of miR-150-5p. C-33A and HeLa cells were utilized to determine the function of miR-150-5p through targeting SRCIN1. Among the aberrantly expressed miRNAs, miR-150-5p was significantly revealed differential expression in cervical carcinoma cell lines and was closely relevant to cell growth regulation. Furthermore, we found that SRCIN1 overexpression could obviously inhibit the proliferation and EMT of cervical cancer cells triggered by miR-150-5p mimics as well as accelerated the apoptosis of cervical carcinoma cells. In conclusion, our data demonstrated that miR-150-5p could promote the proliferation and EMT of cervical carcinoma cells via targeting SRCIN1. Thus, miR-150-5p may hold a promise as a prognostic biomarker and potential therapeutic target for cervical carcinoma.
 ...
PMID:miR-150-5p promotes the proliferation and epithelial-mesenchymal transition of cervical carcinoma cells via targeting SRCIN1. 3067 84