Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.

Cancer is a deadly disease worldwide, with an anticipated 19.3 million new cases and 10.0 million deaths occurring in 2020 according to GLOBOCAN 2020. It is well established that carcinogenesis and cancer development are strongly linked to genetic changes and post-translational modifications (PTMs). An important PTM process, ubiquitination, regulates every aspect of cellular activity, and the crucial enzymes in the ubiquitination process are E3 ubiquitin ligases (E3s) that affect substrate specificity and must therefore be carefully regulated. A surfeit of studies suggests that, among the E3 ubiquitin ligases, neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4)/NEDD4-like E3 ligases show key functions in cellular processes by controlling subsequent protein degradation and substrate ubiquitination. In addition, it was demonstrated that NEDD4 mainly acts as an oncogene in various cancers, but also plays a tumor-suppressive role in some cancers. In this review, to comprehend the proper function of NEDD4 in cancer development, we summarize its function, both its tumor-suppressive and oncogenic role, in multiple types of malignancies. Moreover, we briefly explain the role of NEDD4 in carcinogenesis and progression, including cell survival, cell proliferation, autophagy, cell migration, invasion, metastasis, epithelial-mesenchymal transition (EMT), chemoresistance, and multiple signaling pathways. In addition, we briefly explain the significance of NEDD4 as a possible target for cancer treatment. Therefore, we conclude that targeting NEDD4 as a therapeutic method for treating human tumors could be a practical possibility.

Demystifying the Functional Role of Nuclear Receptors in Esophageal Cancer.

Esophageal cancer (EC), an aggressive and poorly understood disease, is one of the top causes of cancer-related fatalities. GLOBOCAN 2020 reports that there are 544,076 deaths and 604,100 new cases expected worldwide. Even though there are various advancements in treatment procedures, this cancer has been reported as one of the most difficult cancers to cure, and to increase patient survival; treatment targets still need to be established. Nuclear receptors (NRs) are a type of transcription factor, which has a key role in several biological processes such as reproduction, development, cellular differentiation, stress response, immunity, metabolism, lipids, and drugs, and are essential regulators of several diseases, including cancer. Numerous studies have demonstrated the importance of NRs in tumor immunology and proved the well-known roles of multiple NRs in modulating proliferation, differentiation, and apoptosis. There are surplus of studies conducted on NRs and their implications in EC, but only a few studies have demonstrated the diagnostic and prognostic potential of NRs. Therefore, there is still a paucity of the role of NRs and different ways to target them in EC cells to stop them from spreading malignancy. This review emphasizes the significance of NRs in EC by discussing their diverse agonists as well as antagonists and their response to tumor progression. Additionally, we emphasize NRs' potential to serve as a novel therapeutic target and their capacity to treat and prevent EC.

The emerging role of human papillomavirus in lung cancer.

Lung cancer stands as one of the most lethal diseases and is the foremost cause of cancer-related mortalities worldwide. The pathophysiology of lung cancer is multifaceted, and it includes multiple cell signaling pathways and other complex factors such as oxidative stress and genetics. The association of HPV with lung carcinogenesis was first proposed in 1979, and since then, scientists worldwide have been putting forward several hypotheses to establish a relationship between this virus and lung cancer. Although studies have reported the presence of HPV in lung cancer, the exact mechanism of entry and the route of transmission have not been elucidated clearly till date. Numerous studies across the globe have detected differentially expressed HPV oncoproteins in lung cancer patients and found their association with the critical cell signaling pathways that leads to the development and progression of lung cancer. Many reports have also provided evidence stating the involvement of HPV in determining the survival status of lung cancer patients. The present review recapitulates the studies evincing the association of HPV and lung cancer, its route of transmission and mechanism of action; the detection of the virus and treatment opportunities for HPV-positive lung cancer; and the severity associated with this disease. Therefore, this will provide an explicit idea and would help to develop preventive measures and specific as well as effective treatment for HPV-associated lung carcinogenesis.

Delineating the role of nuclear receptors in colorectal cancer, a focused review.

Colorectal cancer (CRC) stands as one of the most prevalent form of cancer globally, causing a significant number of deaths, surpassing 0.9 million in the year 2020. According to GLOBOCAN 2020, CRC ranks third in incidence and second in mortality in both males and females. Despite extensive studies over the years, there is still a need to establish novel therapeutic targets to enhance the patients' survival rate in CRC. Nuclear receptors (NRs) are ligand-activated transcription factors (TFs) that regulate numerous essential biological processes such as differentiation, development, physiology, reproduction, and cellular metabolism. Dysregulation and anomalous expression of different NRs has led to multiple alterations, such as impaired signaling cascades, mutations, and epigenetic changes, leading to various diseases, including cancer. It has been observed that differential expression of various NRs might lead to the initiation and progression of CRC, and are correlated with poor survival outcomes in CRC patients. Despite numerous studies on the mechanism and role of NRs in this cancer, it remains of significant scientific interest primarily due to the diverse functions that various NRs exhibit in regulating key hallmarks of this cancer. Thus, modulating the expression of NRs with their agonists and antagonists, based on their expression levels, holds an immense prospect in the diagnosis, prognosis, and therapeutical modalities of CRC. In this review, we primarily focus on the role and mechanism of NRs in the pathogenesis of CRC and emphasized the significance of targeting these NRs using a variety of agents, which may represent a novel and effective strategy for the prevention and treatment of this cancer.