UbcH10 a Major Actor in Cancerogenesis and a Potential Tool for Diagnosis and Therapy

Abstract

Malignant transformation is a multistep process in which several molecular entities become dysregulated and result in dysfunction in the regulation of cell proliferation. In past years, scientists have gradually dissected the pathways involved in the regulation of the cell cycle. The mitotic ubiquitin-conjugating enzymes UbcH10, has been extensively studied since its cloning and characterization and it has been identified as a constantly overexpressed factor in many types of cancer. In this paper, we have reviewed the literature about UbcH10 in human cancer, pointing out the association between its overexpression and exacerbation of cancer phenotype. Moreover, many recalled studied demonstrated how immunohistochemistry or RT-PCR analysis can distinguish normal tissues and benign lesions from malignant neoplasms. In other experimental studies, many of the consequences of UbcH10 overexpression, such as increased proliferation, metastasizing, cancer progression and resistance to anticancer drugs are reversed through gene silencing techniques. In recent years, many authors have defined UbcH10 evaluation in cancer patients as a useful tool for diagnosis and therapy. This opinion is shared by the authors who advertise how it would be useful to start using in clinical practice the notions acquired about this important moleculein the carcinogenesis of many human malignancies.

Keywords: UbcH10; cancer; cell cycle control; gene silencing; immunohistochemistry; prognosis; therapy; ubiquitin proteasome system.

Figure 1

UbcH10 is together with Ube2S, the ubiquitin-conjugating enzymes (E2) partner of anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligases (E3) complex. UbcH10 is devoted to ubiquitination priming and multi ubiquitination, while Ube2S presides to further ubiquitin chain elongation. UbcH10 overexpression has been detected in samples of diverse solid tumors or hematologic cancers as well as in experimental models. Experimental silencing of UBE2C mRNA levels allowed to find a link between its overexpression and worsening of malignant characteristics.