The Role of Transglutaminase 2 (TG2) in Definition of Cancer Hallmarks.

Over the past three decades, TGM2, a stress-responsive gene encoding transglutaminase 2 (TG2) has been identified as one of the several genes that may be involved in carcinogenesis and cancer physiology. TG2 is a pleiotropic calcium-dependent enzyme belonging to the transglutaminase family of enzymes, which post-translationally modify glutaminyl and lysyl side chains on the surface of both in vivo and in vitro substrate proteins. Unlike other members of the transglutaminase family, TG2 has additional Ca2+-independent enzymatic and non-enzymatic activities, which have been directly or indirectly implicated in diverse cellular physiological events, including cell growth and differentiation, cell adhesion and morphology, extracellular matrix stabilization, wound healing, cellular development, receptor-mediated endocytosis, apoptosis, and disease pathology. TG2 has specialized biochemical, structural and functional elements, wide tissue distribution and subcellular localisation, as well as broad substrate specificity. These specialised features of TG2 account for its multiple patho-physiological functionalities. Considering the multiplicity of TG2 functions and its importance in disease pathology, including cancer; we have reviewed herein, the importance of TG2 in the definition of the hallmark capabilities of cancer cells. This was done with the view to deepen our understanding of the role of TG2 in carcinogenesis and recapitulating its potential as a therapeutic target for cancer treatment.

History and Biology of Transglutaminase 2: A Synopsis.

Transglutaminase 2 (TG2) belongs to the family of transglutaminase, a large group of intracellular and extracellular enzymes that primarily catalyze the Ca2+-dependent posttranslational modification of proteins. Discovery of the first transglutaminase in the early 1920s, has subsequently lead to the identification of nine members of the enzyme family including TG2; the most abundant, most popular and most studied member of the transglutaminase enzyme family. The popularity of TG2 is due to its uniqueness amongst other members of the Transglutaminase (Tgase) family. Its difference from other Tgase family members is due to its specialized structural and biochemical activities; abundant tissue distribution and sub-cellular localization; and multi-functionality and physiology. The growing interests in TG2 and related research has resulted to an attendant mega-research output; and the need to produce a well-structured compilation of data on this popular enzyme has arisen. It is against this background, that we have compiled herein, a synopsis of available literature on TG2 history, structural and biochemical activities, tissue distribution, and physiology. This was done with the view to providing a compendium of background information that could be handy to researchers and new interest in the field of TG2 research.

Dissecting Biology of Solid Tumour: The Microenvironment and Cancer Progression.

Focus on cancer therapy is experiencing a major paradigm shift from ways of attacking tumor cells to a strategy for specifically targeting the tumor microenvironment (TME). This approach requires a comprehensive understanding of roles of each component of the tumor environment. A description of the tumor microenvironment and its impact on tumor progression is presented here. Available studies indicate that both tumor/epithelial and stroma characteristics play important roles in cancer progression. Details of this work show that different components of the tumor microenvironment contribute towards cancer progression and clearly suggest a role for use of combination therapies for tight tumor control.

Androgen Ablation Therapy and Prostate Cancer: An Update.

It is now generally accepted that prostate cancer is the leading form of cancer in men. Current evidence indicates that countries including America and West Africa have more cases of aggressive progressive prostate cancer. Many treatment strategies have been used in management of prostate cancer. Since the discovery of androgen deprivation protocol seventy years ago, more treatment strategies have been reported which added more values to treatment outcome. However, death from this disease is due to resistance to androgen ablation therapy (AAT). Until recently, treatment of patients with disseminated prostate cancer was based on modalities that reduce AR signalling, either by direct androgen depletion (castration, e.g., surgical orchiectomy, luteinizing hormonereleasing hormone agonists), by blockage of the androgen receptor (AR) (e.g., flutamide, bicalutamide), or by combinations. In literature there is wide range of reports on diverse treatment strategies for prostate cancer; this often lead to serious confusion among clinicians and scientists, especially those new to the field. This study reviewed all the current available treatment strategies for androgen ablation therapy in management of hormone sensitive progressive prostate cancer, and highlights the merits and challenges involved in each of the treatments options. Thus, providing a summary of wide range of available literature on hormone management of prostate cancer and brings the scientists and clinicians to a focus using the best available evidence-based approach.