Lef/Tcf Full Length Expression And Their Isoforms Vary

I was deeply touched when my grandfather was diagnosed with widespread colon cancer several years ago. Being naïve at the time, I thought “why is cancer so bad, can’t it be cured just like the flu?” From my Biology and Genetics courses, I realized that cancer was a complex problem that was not fully understood, despite many advances. To my surprise, I found that cancer was the second leading cause of death according to the CDC website. This sobering statistic spiked my curiosity and led me deeper into the topic. I became intrigued by cellular pathways and how missteps in the pathways could result in cancer. It also struck me that most discoveries were confined to labs and research papers without ever reaching patients. I decided to become a scientist and do my part to advance the understanding of

Figure 2 [3]: The role of cadherin and catenin in the binding of cancer cells to the endothelium.

In vitro: ICG-001 specifically inhibits T-cell factor/β-catenin transcription in a cyclicAMP responseelement binding protein binding protein (CBP)-dependent fashion. Furthermore, ICG-001 blocks selectively the β-catenin/CBP interaction without interfering with the β-catenin/p300 interaction

They have identified key molecules that regulate the cell cycle in all eukaryotic organisms, including yeasts, plants, animals and human. These fundamental discoveries have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. This may in the long-term open

A large body of literature has documented hyperactivated AKT signaling in human solid tumors and hematological malignancies[34]. The PI3K/AKT/mTOR signaling pathway plays an important role in HCC and is activated in 30%–50% of HCC[35]. Sorafenib does not target this pathway. AKT/mTOR is critical for regulating growth and proliferation in any cell type. Data from HCC clinical trials have revealed that AKT/mTOR pathway is upregulated upon treatment and therefore the cancer acquires resistance to therapy. Cyclin D1 is a downstream target of AKT, which directly regulates cell cycle progression. Of the three highly conserved AKT isoforms, AKT1 is involved in regulating cell proliferation[36]. Accumulating research suggests that PI3K/AKT activation after sorafenib treatment plays a pivotal role in tumor progression in HCC. p-AKT levels increase in HCC cell lines after treating them with sorafenib [11, 37]. Targeting AKT1 will also suppress the activity of its downstream effector pathway

In this research paper, the experimental design was based around the relationship to CCND1 to breast cancer. CCND1 is present during the G1 phase of the mitosis cell cycle. Which occurs right before the S phase. If the CCND1 has a malfunction then the rest of the cell cycle will not finish off correctly into normal functioning cells. The research paper also noted that tumor heterogeneity is a critical issue and there is a hard time treating the tumors because it rejects most of the cell therapy treatments.

Haller et al. (2010), have just defined the connection between p16 overexpression in the cytoplasm and p16 downregulation in the nucleus, with bad prognosis in gastrointestinal stromal tumor (24). Intriguingly, p16 downregulation in the nucleus was connected with E2F overexpression. On the other hand, p16 overexpression in the cytoplasm did not show any link with expression of E2F. These outcomes help support the proposition that p16 has various jobs in distinctive subcellular locations. It also supports the idea that nuclear p16 helps regulate control of the cell cycle. Remarkably, other regulators of the cell cycle typically found in the nucleus have been seen to be translocated to the cytoplasm in various tumors, like PTEN or p27. Both of these proteins have the capability to carry out distinctive activities from other subcellular locations (58).

If the APC protein were to experience a nonsense mutation, the most common mutation in regards to this specific genetic disease, the destruction complex would not perform correctly and the wnt-signaling pathway would be stimulated. Problems begin to arise when “the Wnt/Beta-catenin pathway is activated [by] a Wnt ligand [binding] to seven-pass transmembrane Frizzled receptor and its co-receptor, low-density lipoprotein related protein 6 (LRP6) or its close relative LRP5” (MacDonald, et. al 2009). Once the wnt-signaling pathway is stimulated, a Wnt-Fz-LRP6 complex forms and takes in the Dishevelled (Dvl) protein, resulting in the phosphorylation and activation of the recruitment of the axin complex, destruction complex, to the receptors. (MacDonald, et al 2009). Due to the phosphorylation within the Wnt-Fz-LRP6 complex, the axin complex is not able to phosphorylate Beta-Catenin, which leads to the excessive accumulation of the protein in the cytoplasm. Researchers witnessed the development of numerous intestinal adenomas in transgenic mice with stabilized mutant Beta-catenin, therefore the results suggest that dysregulation of Beta-catenin is a key oncogenic event that follows the loss of APC function. (Tarapore, et. al 2011). The loss of the destruction complex’s normal activities results in elevated levels of Beta-catenin and downstream effectors such as CCND1,

As discussed, galectin-8 is has different functions such as cell growth and apoptosis. When galectin-8 interacts with different integrins, high affinity interactions are formed. When galectin-8 is soluble, it inhibits the cell cycle and prompts the arrest of cell growth [6]. This is caused by a 4-5-fold increase in p21, which is a cyclin-dependent kinase inhibitor [6]. An increase in c-Junc-n-terminal kinases (JNK) and protein kinase B (PKB) activities cause an increase in the levels of p21. When galectin-8 cDNA is transfected into cells of human lung carcinoma, the inhibition of colon formation is noticed; this suggests that when galectin-8 is overexpressed, it may inhibit cell growth [6]. An experiment was done to examine the effects of galectin-8. There were multiple procedures that took place in this experiment; the generation of antibodies against galectin-8, the creation of cell cultures with human carcinoma cells, generation of GFP-galectin-8, generation of GHO cells overexpressing a mutant form of SEK1, the preparation of cell extracts, the binding of galectin-8 to Lactosyl-Agarose beads, Thymidine incorporation, apoptosis, PCR, and a Northern Blot Analysis.

TTF-1 ( Nkx2-1), a homeodomain-containing nuclear transcription factor has been a marker in the diagnosis of lung adenocarcinomas and in differentiating them from tumors of other origin.(1) Nkx2-1 is known for its transcriptional activity in the developing lung, thyroid and forebrain. Altered expression of TTF-1 resulting from mutations, polymorphisms and/or epigenetic modifications can predispose an individual to developmental disorders including thyroid dygenesis and thyroid cancer.(2) Mutations of the TTF-1 gene that induce haploinsufficiency may endow a negative effect on the wild-type gene.(3) Nkx2.1 is essentially involved with morphogenesis in the lung by modulating epithelial-mesenchymal interaction. Mouse models with functional

Proliferating cells must progress through 4 phases of cell cycle to divide (G1, S, G2 and M); however, they may exit cell cycle and enter quiescence (G0) when stressed or deprived of their biological stimuli (for example in breast cancer with estrogen deprivation)7, 8. Cyclin-dependent kinases (CDKs) play a key role in controlling cell cycle progression. Among these kinases, CDK4/6 is the key regulator of G1 to S transition by controlling transcription of genes necessary for cell cycle progression. This kinase is activated upon binding to cyclin D, leading to expression of genes required for S-phase entry9. This tightly regulated cyclin D-CDK4/6 complex is

The level of activity of Gli genes, and thus Hh-pathway activation, determines skin tumor phenotype: high level signaling is shown to result in BCC and low-level signaling is shown to result in follicular derived tumors such as basaloid follicular hamartoma (BFH) (2). Gli2 is involved in the expression of cell cycle regulation genes in the Shh-pathway such as E2F1, CCND1, CDC2 and epidermal differential genes. Over-expression of Gli2 causes the up-regulation of such cell cycle regulation genes in developing hair follicles. Shh-activation most specifically promotes degradation of the p53 tumor suppressor gene (2), thus repressing transcription of p21, a key suppressor of cyclin E in cell-cycle regulation. Thus, G1 arrest is overrode, and the inability to control cell cycle is promoted: a key feature of cancer. Sufu and Kif7 have overlapping functions in regulating Gli transcription factors. Specifically, Gli2 forms a complex with Sufu to prevent transcriptional activity via preventing accumulation of Gli2 transcriptional factors into the nucleus, thus repressing Hh pathway transduction (3). Sufu also plays a role in stabilizing Gli2 by blocking Spop, an E3 ligase involved in degradation of Gli2 (3). In keratinocytes, Kif7

In about a third of primary ovarian tumour, EEF1A2 is raised in copy number, and whilst EEF1A2 mRNA is not measurable in normal ovarian epithelium, the rate of EEF1A2 mRNA is increased in a third of ovarian tumours. It appears here that EEF1A2 is an important ovarian cancer oncogene (Lee, 2003). Moreover, when the eEF1A2 expression is induced in human ovarian cell line, the eEF1A2 expressing cell line is more tumorigenic; this proves that eEF1A2 promotes malignancy in ovarian cells (Anand et al., 2002). EEF1A2 is also an oncogene in lung adenocarcinoma (Li et al., 2006). And in a high proportion of pancreatic carcinoma, eEF1A2 is up-regulated while it is just a little bit expressed in normal pancreas (Cao et al., 2009). EEF1A2 over-expression seems to enhance cell growth, proliferation, motility, survival and invasion of pancreatic cancer cells (Cao et al., 2009). In two third of breast cancer, EEF1A2 is over-expressed, which indicates that eEF1A2 might be an oncoprotein (Tomlinson et al., 2005). But interestingly, it has been shown that eEF1A2 also augurs

There are all kinds of tumor markers of colon cancer, the classification is different. Some classic markers such as CA242, CA199, CA72-4, and CEA have been applied to clinical studies, and Some classic markers ,such as TGF,have the potential to serve as markers for colon cancer Clinical application.

Wnt3a is highly expressed in human scirrhous gastric carcinoma 44As3 cells with highly metastatic derivatives, advanced prostate cancer cells, and activating transcription factor (ATF3)-induced mammary tumors. Wnt3a expression is higher in oral squamous cell carcinoma compared with control non-malignant tissues (He et al, 2015). A study reports that the canonical Wnt signaling pathway and DPAGT1 function in a positive feedback loop. Previously, they have shown that both β catenin and γ- catenins bind to the DPGAT1 promoter and hence DPAGT1 was a target of the canonical Wnt signaling pathway (Sengupta et al, 2010). Two cell lines and five OSCC tissue samples with paired adjacent normal epithelia were analysed. The OSCC tissues over expressed DPGAT1 three to four fold when compared to normal tissues with β and γ- catenins bound to the DPGAT1 promoter. There was an increased expression of Wnt 3 and decreased expression of Dkk 1, with down regulation of E cadherin and activation of a positive feedback loop between Wnt signaling and DPGAT1(Jamal et al, 2012).