Analysis Of Podocalyxin And Ezrin In Cancer

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

An effective breast cancer treatment in some women can be traced to the root of the disease. Some of the most aggressive form of breast cancers are caused by a transmembrane receptor protein known as Human Epidermal Growth Factor Receptor 2 (HER2) which is a member of the HER family of receptor tyrosine kinase. Approximately 20,000 HER2 receptor are normally expressed on surface of healthy breast cell however, in about 25% of breast cancer cells the HER2 protein is overexpressed resulting in tumour cells with as many as over 2 million receptors present on their surface. This cancer is known as HER2 positive (HER2+). The effect of HER2 overexpression is an increase in receptor mediated intracellular signalling causing the cell

As the cells change, it begins to divide rapidly causing a tumor to form. The term “breast cancer” refers to a malignant tumor that has developed from cells in the breast. Breast cancer can begin in different areas of the breast, or in some cases, the tissues in between. There are many different types of breast cancer, including non-invasive, invasive, recurrent, metastatic breast cancer, as well as the intrinsic or molecular subtypes of breast cancer. Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20-30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality.

Cancer is listed as the second most common cause of death in western countries; particularly, in adults. Though it has a long antiquity, its prevalence and incidence today is pervasive and the war on cancer has not been promising. Malignant neoplasia is characterized by uncontrolled growth and the ability to metastasize or spread from the original site. Cancer results from mutations that promote cell proliferation and inhibit cell adhesion (metastasis). According to the National Cancer Institute (2016), “Cancer can also spread regionally,

The epidermal growth factor receptor (EGFR) is the cell-surface receptor for extracellular protein ligands. EGFR family has four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu, Her 3 and Her 4. Mutations affecting EGFR expression or activity could lead to cancer.

Cancer cells can intrude other tissues in different forms (sheets, clusters, or singular cells) (INSERT REFERENCE HERE). As the cancer cells manifest, its morphology will change, which includes epithelial-mesenchymal transition (EMT), mesenchymal to amoeboid transition (MAT) and collective to amoeboid transition (CAT).

Signaling pathways that result in cell migration are often useful in understanding how cancer cells metastasize. The researchers of Swaminathan et al., 2016 examine how adhesion site assembly occurs while Nader et al., 2016 focuses primarily on the adhesion turnover both are fundamental processes in cell migration. Integrins play a dominant role in nascent integrin-mediated adhesions (NAs) which are important in lamellipodium protrusion and generating traction at focal adhesion points involved in cell motility. Integrins have been extensively studied and are linked to wound healing as well as metastasis in cancer cells (Lawson et al., 2012). When extracellular signals, either chemical or physical, contact the cell surface it triggers a response that induces movement. If the signaling molecule is a growth factor (ex. Epidermal Growth Factor) it could activate a GTPase protein coupled receptor (GPCR). The next is a signal cascade often led by Rabs or Ras (small G-proteins) proteins that are powered by GTPase hydrolysis, which often recruits and activates Wiskott–Aldrich Syndrome protein (WASP) or Scar. Previous studies identified cancer cell that use Rab-coupling to control cell motility by regulating B-intgrins trafficking (Nader et al., 2016). WASP recruits Actin related protein 2 and 3 (Arp2/3) complex to the cell membrane and activates it

The uncontrollable spread of cancer is the principal event which leads to the death in individuals with cancer and it is the greatest barrier of developing cures for cancer. Metastasis is the progressive spread of malignant cancer cells from the primary tumour to secondary organ in distant sites and this potential is dependent on the specific microenvironment which support them to complete each step of the metastatic process (Poste & Fidler 1980). To understand the molecular basis of metastasis, investigators have now separated the complex and highly selective metastasis process into series of steps to try and solve the problems cause by

Tumor is a complex tissue comprising not only the malignant cells, but the surrounding stroma as well. Stroma is the microenvironment in which a tumor originates and progresses as a malignant disease. The tumor microenvironment plays critical roles in cancer pathogenesis controlling multiple events associated with the tumor development, such as tumor cell proliferation, invasion, metastasis and angiogenesis, and thus could be a focus in developing therapeutic approaches. It also can limit the access of therapeutics to the tumor, alter drug metabolism and contribute to the development of drug resistance. Because of their role in all the stages of tumor development, stromal elements represent attractive therapeutic targets. Manipulating host-tumor

Through the successes of molecular biology in the last 30 more years, we now understand that oncogenes and tumor suppressor genes encode many cellular signal pathways that not only sustain cancer proliferation but also reprogram cancer energy metabolism to meet the biosynthetic challenge associated with the cancer cells growth and proliferation (Hanahan and Weinberg, 2011; Vander Heiden et al., 2009; Ward and Thompson, 2012a). Many signaling pathways including PI3K/Akt/mTORC1 and HIF are involved in cancer metabolic reprograming for cellular biosynthesis (Jones and Thompson, 2009; Ward and Thompson, 2012a, b). Furthermore, oncogenes and tumor suppressors have been found to be critical components of these metabolic

The other influential components such as PI3K, ERK, and Ras have been previously explored in multiple cancer types. However, the influential components consist of the most important drug candidates that block cell proliferation in cancer cells. Some of these components have been associated with the drug resistance. For example, in non-small cell lung cancer, EGFR showed mutation in its kinase domain, Epithelial–mesenchymal transition, and mechanisms to develop resistance to gefitinib [35]. In colorectal, and head and neck cancers KRAS mutation, EGFR-S492R mutation, and increased ErBb signaling are responsible for resistance

Cancer remains one of the most devastating diseases in the world. Tumor is the uncontrolled development and spreading of cells that may affect almost any tissue of the body. In this regard, more than 10 million individuals every year are determined to have cancer around the world (reference). It is evaluated that there will be 15 million new cases by the year 2020 (Reference). Around the world, every year cancer causes six million passings (12% of all deaths). Carcinogenesis is a multistep process regulated by genetic and epigenetic changes; disrupting several signaling pathways regulating cellular growth, apoptosis, differentiation and angiogenesis [1,2]. As a normal routine, mammalian cells grow, divide, and die in an orderly fashion. However,

CN’s dimeric structure results in high reactivity in platelet protein phosphorylation, allowing CN to bind to IIb3 and inhibiting platelet aggregation. It is also known that CN is able to bind to 1 and 3 subclasses, inhibiting many types of integrins (Lin et al. 2010). Research has shown that the two integrins that are expressed in angiogenesis and cancer metastasis are v3 and v5. Blocking v5 results in blocking the vascular endothelial growth factor, or VEGF, angiogenesis because of its involvement in cell adhesion. This integrin requires an insulin growth factor to activate to mediate cell migration. Zhou et al. (2000) has shown that CN binding to vitronectin receptors allows the inhibition of melanoma and breast cancer cells to vitronectin. In addition, v3 commonly mediates tumor cell adhesion to vitronectin. However, antagonists to this integrin can inhibit angiogenesis in endothelial cells, with CN acting as an antagonist. Many studies have tested the efficacy of CN on tumors from breast cancer, prostate cancer, and bladder cancer. For example, CN was able to inhibit the adhesion of T24 bladder carcinoma cells to vitronectin (Zhou et

Tumor angiogenesis refers to an attribute of tumor cells residing with the capacity to elicit continuously the growth of new capillary endothelium. Tumor angiogenesis occurs by recruitment of endothelial cell precursor or by sprouting of existing capillaries as in physiologic angiogenesis. Angiogenesis (the formation of new blood vessels) is implicated in the pathogenesis of many chronic diseases including cancer. Angiogenesis in the tumor mass permits growth and invasiveness of the cancer cells as it is believed to be essential for the delivery of essential nutrients and oxygen to the tumor microenvironment. Clustered evidence suggests that angiogenesis is a critical event in the progression of solid tumors because tumor growth beyond 2 to

(2012) and Yang et al. (2013). Furthermore, EMMPRIN expression showed a predominantly peripheral/ basal distribution pattern in the tumor islands in most of our cases. This was reported in other studies (Monterio et al 2014) suggesting a more frequent distribution of this receptor in tumor cells with a more proliferative phenotype. This expression pattern can be attributed to the structure of EMMPRIN, as it has a cytoplasmic and membranous domain which was previously described by Iacono et al. (2007).