Human Kallikrein Related Peptidases ( Klks )

A key factor in the development of tumors is the ability of cancerous cells to evade recognition from the bodies’ natural defense against cancer, the immune system. Immunotherapies effectively block the pathways that shield cancerous cells from being identified, and thus the promote the bodies own anti-tumor response. However, one challenge to immunotherapy has been its combination with chemotherapy, the mainstay of cancer treatment. While chemotherapy is extremely effective in stopping the rapid division of cancerous cells, its toxic immunosuppressive side-effect make it difficult to combine with

Imagine your child dying a few months after they are born because of the genes you passed down to them. This is possible with many genetic diseases; one such disease can be Krabbe disease. Krabbe disease changes many aspects of a diagnosed person’s life because of the troubling and debilitating side effects. Children with Krabbe disease might not be able to complete daily activities. This can affect not only the child but also the people around them.

What is Krabbe disease? Krabbe disease, also known as globoid cell leukodystrophy, is a rare but deadly disease. It is caused by the inability to create enough of a substance called galactosylceramidase, which is needed to make myelin. This leads to a buildup of toxic substances in cells that produce the myelin sheath and to a progressive loss of myelin that covers many nerves. Myelin acts as a protective covering for cells and nerves and without it, cells and nerves in the brain can’t function properly.

The specific metabolic disorder that I picked for this discussion is Krabbe Disease or globoid cell leukodystrophy. The disease destroys the protective coating of nerve cells in the brain and throughout the body causing the nerve cells to stop responding or react unpredictably. The disease is caused by a person receiving two copies of a mutated gene that results in severely curtailed production of an enzyme called galactocerebrosidase (GALC) (Krabbe disease, n.d.). This enzyme is responsible for breaking down certain substances in a cell's recycling center. Unfortunately, in Krabbe disease, not enough GALC was produced so the cells begin accumulating fats called galactolipids which normally are responsible for maintaining the protective coating

Krabbe disease is a disorder in the nervous system in which the patient becomes unable to function correctly. This enzyme deficiency impairs the growth and maintenance of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. A large cell of a primary germ is found clustered together in the space between the skull and the brain causing it to destroy the cells. Although, this disease generally directed at infants it may also develop in an older child or adult.

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 prostate gland is an egg-sized organ that rings the male urethra. The secretions of the prostate give nutrients to the semen. Prostate cancer is the most commonly diagnosed cancer and the second most common cause of cancer death in men. (Ernstoff,Heaney,Peschel,1998,pviii) Like all cancers, prostate cancer is an uncontrolled cell production in a particular organ or area of the body. In the case of prostate cancer, these cells begin to split impulsively in the prostate and form tumors. As these tumors begin to grow they begin to use up oxygen from other healthy cells and surrounding tissue. Not only do these tumors take up oxygen from other cells, they secrete protein signals that initiate the formation of new

BYL719 is a specific PI3Kα inhibitor. The PI3K pathway deregulation occurs in more than 50% of breast cancers. Mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K has been reported to contribute to resistance to endocrine and anti-HER2 therapies.

In the United States alone, a genetic disorder known as Phenylketonuria (PKU) occurs in every 1 in 10,000 newborns, and has the capacity to cause severe mental deceleration. The causative agent of PKU is a single mutation in the PAH gene, which triggers the build-up of the amino acid phenylalanine. Thanks to discoveries made over the last century, newborns are screened for the disorder at birth, and thus treatment can start promptly if needed. As of now, there is no cure for PKU, only a restrictive diet to reduce symptoms.

Trypsin aids in digestion by degrading peptides in food (SITE). The expression of metabolic enzymes, such as trypsinogen, is up-regulated with the onset of KRAS induced pancreatic ductal adenocarcinomas [5]. In order to maintain the integrity of the endothelial layer of the duct, the expression of SPINK, a serine protease inhibitor, is also up-regulated SPINK is co-expressed with trypsinogen to prevent premature activation of the trypsinogen within the pancreas as this may damage the pancreas [12]. SPINK has also been shown to have growth enhancing effects, a pro-survival effect, within the pancreas (SITE) As a result, we expect SPINK expression to be elevated in tumorigenesis. As SPINK expression is enhanced, trypsin activation will decrease and most synthesized trypsinogen will stay in its inactive form. With this notion, we believe that, when the ratio of SPINK to trypsin surpasses a particular limit, it can be used as a marker for early detection of PDAC since their expressions are both altered (increasing inhibitor, increasing trypsin in zymogen (trypsinogen) form which implies decreasing active trypsin) in a fashion that when put together seems to be unique and selective to PDAC

Cancer metastasis in the main character and hallmark of cancer progression [6]. Metastasis is a multi-step process beginning from detachments of cancer cells from the primary tumor, disruption of the basement membrane for invading to surrounding tissue. Subsequently, the cancer cells able entry to the blood and lymphatic system to spread into other part of the body and extravasation for growth and proliferate in distant sites [7]. Matrix metalloproteinase (MMP) is a zinc-dependent endopeptidase which responsible in degradation the component of extracellular matrix (ECM) proteins including collagen, elastin, fibronectin. MMP can secrete by inflammatory cells, osteoblast, fibroblast, and also cancer cells. MMP has a pivotal role in promoting

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

The ability of cancerous cells to migrate from their primary site and invade a secondary site is a hallmark of malignant progression. The invasive potential of a tumor hinges on the rigidity of its epithelial microenvironment in vivo, or the stiffness of the matrix on which the cells are grown in vitro. The serine/threonine protein kinase Cα (PKCα) promotes cell movement and contributes to tumor invasion, partially due to its activity on two newly discovered substrates, CEP4 and α6-tubulin. We set out to characterize the role of these PKCα substrates in the invasive phenotype of an aggressive metastatic mammary carcinoma cell line LM2-4175. We hypothesized that phosphorylation-resistant mutants of CEP4 and α6-tubulin would decrease the invasive phenotype. To test this, we transiently transfected LM2-4175 cells with either wild type or phosphorylation-resistant CEP4 or α6-tubulin and studied their migratory efficiency in transwells fitted with matrices of differing stiffness. In parallel, cells were treated with a PKC activator. As predicted, migration was potentiated by stiffer matrices under all conditions, with the exception of cells transfected with phosphorylation resistant CEP4 and α6-tubulin where the invasion in the softer matrix was greater. Furthering our understanding of the individual contributions of substrates of PKCα holds clinical promise, as it will permit the development of novel targeted therapeutics to curb cell migration and metastasis.

The luminal A subtype of breast cancer had the highest frequency of PIK3CA mutation (45%), and the basal subtype had the lowest (9%). Additional identified aberrations resulting in the dysregulation of the PI3K/mTOR pathway include Akt and PTEN mutations, or loss of PTEN protein [11,12].

This activated dimeric PKM2 has a property distinct from tetrameric PKM2 found in non-cancer cells. The active dimeric PKM2 can phosphorylate protein substrates using phosphoenolpyruvate (PEP) as a phosphate donor. Several proteins phosphorylated by the PKM2-SAICAR complex include Erk1/2 and histone H3.1. These phosphorylations activate the proliferation signaling and induces expression of MYC and others. Thus, the altered level of SAICAR in cancer cells activates proliferation signaling and induce epigenetic changes. As a result, the PKM2-SAICAR interaction promotes the survival and the proliferation of cancer cells.