HIPK2 expression in progression of cutaneous epithelial neoplasm

Abstract

HIPK2 expression tends to be decreased along tumor progression and may be involved with the invasive potential, suggesting a possible tumor suppressor role for HIPK2.

HIPK2 Overexpression and Its Prognostic Role in Human Papillomavirus-Positive Tonsillar Squamous Cell Carcinoma

“…Staining was carried out according to the manufacturer's protocol on the BenchMark XT automated immunohistochemistry stainer (Ventana Medical Systems, Inc., Tucson, AZ, USA) using the ultraView DAB Kit (Ventana Medical Systems). The primary antibodies were HIPK2 (1 : 100; Abcam, Cambridge, UK) and p53 (1 : 500; Novocastra, Newcastle, UK) and were incubated as previously described [ 18 ].…”

“…HIPK2 is involved in apoptosis and is a central regulator of p53 [ 17 ]. Upon severe DNA damage, activated HIPK2 affects the upregulation of the proapoptotic function of p53 by specifically phosphorylating p53 at serine 46 (Ser46) and repressing its inhibitors, leading to apoptosis [ 12 , 13 , 18 ]. However, in HPV-infected cells, the binding of E6 to HIPK2 inhibits HIPK2-mediated p53 Ser46 phosphorylation by enforcing dissociation of the HIPK2/p53 complex [ 16 ], which prevents apoptosis and thus contributes to carcinogenesis [ 16 ].…”

“…However, in HPV-infected cells, the binding of E6 to HIPK2 inhibits HIPK2-mediated p53 Ser46 phosphorylation by enforcing dissociation of the HIPK2/p53 complex [ 16 ], which prevents apoptosis and thus contributes to carcinogenesis [ 16 ]. The most notable properties of HIPK2 in tumors are that its inhibition or dysfunction leads to impairment of p53 function and the activation of oncogenic pathways that are important for tumor progression, angiogenesis, and resistance to chemotherapy or radiation therapy [ 17 , 18 ], because HIPK2 is activated by several types of genotoxic damaging factors such as UV radiation, ionizing radiation, and antitumor drugs including cisplatin, adriamycin, and roscovitine [ 18 – 21 ]. Conversely, restoration of HIPK2 activity in tumor cells is effective for tumor regression.…”

“…Conversely, restoration of HIPK2 activity in tumor cells is effective for tumor regression. Because of its close relationship with HPV-associated oncogenic pathways and chemoradiation resistance, HIPK2 has recently attracted attention as a potential therapeutic target [ 17 , 18 ].…”

HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation

“…HIPK2 dysregulation has been shown to contribute to proliferative diseases, such as cancer and tissue fibrosis [2, 26–28]. Based on our current knowledge, three possible mechanisms explaining the functional inactivation of HIPK2 have been proposed: the “localization model”, the “optimum model”, and the “PTM model” which foresee, respectively, tight regulations of HIPK2 subcellular localization, protein levels, and PTMs [18].…”