Roles of HMGA proteins in cancer: Expression, pathways, and redundancies
Journal Title: Journal of Modern Human Pathology - Year 2016, Vol 1, Issue 6
Abstract
The expression of the High Mobility Group A (HMGA) proteins, their participation in cancer signalling pathways, and their redundant functions have been reviewed in seven types of cancer: breast, colorectal, prostate, lung, ovarian, thyroid, and brain. The analysis of cell lines and tumours revealed an elevated level of their expression in all fully transformed cancer systems, which represents a step of the main cancer signalling pathways. In breast, colorectal, prostate, and lung cancers Wnt/β-catenin pathway is a master inducer of cell transformation in which are deeply involved HMG A1 and A2 proteins. On the other hand, IL-6/Stat3 pathway is responsible for cancer transformation in breast, lung, and prostate. The expression of HMGA1 in lung and ovarian cancers is due to an active PI3K/Akt pathway. The let-7 family of microRNA represses the expression of HMGA showing specificity by its different forms: the let-7b form is able to inhibit both proteins A1 and A2, the last also inhibited by a, c, d, and g forms. Moreover, both proteins are down-regulated by the repressor couple p53/microRNA-34a. The protein A1 and A2 participate to the Epithelial-Mesenchymal Transition cooperating with the three couples of factors Twist1/2, Snai1/2, and Zeb1/2. Through a combination of pathways, there is the simultaneous presence of high levels of both A1 and A2 together with the expression of other factors: a high co-operating efficiency is reached that supplies the tumour cells with properties of self-renewal, resistance, and invasiveness.
Authors and Affiliations
Giancotti V, Cataldi P, Rizzi C
Keywords
Related Articles
- EP ID EP553324
- DOI 10.14312/2397-6845.2016-8
- Views 53
- Downloads 0
Cul-de-sac splenosis - An unusual location
We present a unique case of splenosis in a 36-year-old female in the posterior cul-de-sac of the lower pelvis, and to our knowledge, has never previously been reported. Her splenosis persisted for years, mis-diagnosed as...
Comparison of the clinicopathologic features of solitary and multifocal papillary thyroid carcinoma and the utility of testing an additional tumor nodule for BRAFV600E in multifocal cases
A retrospective review of the tumor focality and BRAFV600E mutational status of all thyroidectomy cases diagnosed with papillary thyroid carcinoma (PTC) between 1/2010 and 7/2013 was performed. A total of 122 cases were...
Laparoscopic management of primary abdominal pregnancy located on the sigmoid colon: A case report
Abdominal pregnancy (AP) is rare with an estimated incidence of 1/10000 births and only 1.4% of ectopic pregnancies. Primary abdominal pregnancy (PAP) is the least common form of the AP. We present a case of PAP in a 22...
Prevalence of diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndrome (HHS) in emergency departments in Queensland, Australia
A retrospective evaluation was undertaken on the frequency of presentations of DKA and HHS to emergency departments to three major hospitals. Biochemical results, glucose and bicarbonate specifically, and pH, when availa...
Melanoma of unknown primary origin metastasizing to the ovary and breast: Case report and review of literature
Malignant melanoma (MM) simultaneously involving the ovary and breast is a rare manifestation of the disease. We report a case of amelanotic MM of unknown primary origin manifesting as a large ovarian solid mass at its f...