Aurora Kinase A Is Overexpressed in Human Retinoblastoma and Correlates with Histopathologic High-Risk Factors: Implications for Targeted Therapy.

Autor:	Borah NA; The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India; School of Biotechnology, Kalinga Institute of Industrial Technology Deemed to be University, Bhubaneswar, India., Mittal R; Kanupriya Dalmia Ophthalmic Pathology Laboratory, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India., Sucharita S; Kanupriya Dalmia Ophthalmic Pathology Laboratory, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India., Rath S; Ophthalmic Plastics, Orbit and Ocular Oncology Service, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India., Kaliki S; The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Kallam Anji Reddy Campus, Hyderabad, India., Patnaik S; School of Biotechnology, Kalinga Institute of Industrial Technology Deemed to be University, Bhubaneswar, India., Tripathy D; Ophthalmic Plastics, Orbit and Ocular Oncology Service, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India., Reddy MM; The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Mithu Tulsi Chanrai Campus, Bhubaneswar, India; School of Biotechnology, Kalinga Institute of Industrial Technology Deemed to be University, Bhubaneswar, India. Electronic address: mamatha@lvpei.org.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2024 Sep; Vol. 194 (9), pp. 1780-1798. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1016/j.ajpath.2024.05.006
Abstrakt:	Retinoblastoma (RB) is an intraocular malignancy initiated by loss of RB1 function and/or dysregulation of MYCN oncogene. RB is primarily treated with chemotherapy; however, systemic toxicity and long-term adverse effects remain a significant challenge necessitating the identification of specific molecular targets. Aurora kinase A (AURKA), a critical cell cycle regulator, contributes to cancer pathogenesis, especially in RB1-deficient and MYCN-dysregulated tumors. The current immunohistochemistry study in patient specimens (n = 67) indicated that AURKA is overexpressed in RB, and this elevated expression correlates with one or more histopathologic high-risk factors, such as tumor involvement of the optic nerve, choroid, sclera, and/or anterior segment. More specifically, AURKA is ubiquitously expressed in most advanced-stage RB tumors that show a suboptimal response to chemotherapy. shRNA-mediated depletion/pharmacologic inhibition studies in cell lines, patient-derived cells, in vivo xenografts, and enucleated patient specimens confirmed that RB cells are highly sensitive to a lack of functional AURKA. In addition, AURKA and N-myc proto-oncogene protein (MYCN) associate with each other to regulate their levels in RB cells. Overall, these results demonstrate a previously unknown up-regulation of AURKA in RB, facilitated by its crosstalk with MYCN. The elevated levels of this kinase may indicate unfavorable prognosis in tumors refractory to chemotherapy. This study provides a rationale and confirms that therapeutic targeting of elevated AURKA in RB could be a potential treatment approach. Competing Interests: Disclosure Statement None declared. (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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