Journal Article

Anaplastic lymphoma kinase overexpression enhances aggressive phenotypic characteristics of endometrial carcinoma

Nakagawa, Mayu, Nakamura, Yusaku, Harada, Youhei, Ito, Takashi, Fukagawa, Naomi, Matsumoto, Toshihide, Ohhigata, Kensuke, Saegusa, Makoto, Yokoi, Ako, Oguri, Yasuko, Ishibashi, Yu, Hashimura, Miki

2023

Overview

Background Although anaplastic lymphoma kinase (ALK) is overexpressed in several primary solid tumor types, its role in endometrial carcinoma (Em Ca) remains unclear. Methods We evaluated expression of ALK and its related molecules in clinical samples consisting of 168 Em Ca tissues. We also used Em Ca cell lines to evaluate the functional role of ALK. Results Cytoplasmic ALK immunoreactivity in the absence of chromosomal rearrangement was positively correlated with ALK mRNA expression, and was significantly higher in Grade (G) 3 Em Ca than in G1 or G2 tumors. ALK immunoreactivity was also significantly associated with expression of cancer stem cell (CSC)-related molecules (cytoplasmic CD133, ALDH1, Sox2) and neuroendocrine markers (CD56 and synaptophysin). Although the proliferative index was significantly higher in ALK-positive Em Ca when compared to ALK- negative malignancies, there was no association between ALK expression and other clinicopathological factors in this disease. In Em Ca cell lines, full-length ALK overexpression increased proliferation, decreased susceptibility to apoptosis, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown cells. Finally, patients with tumors harboring either wild-type ALK or high ALK mRNA expression had a poorer prognosis than those with either mutant ALK or low ALK mRNA expression. Conclusion Full-length ALK overexpression occurs in a subset of Em Ca, particularly in G3 tumors, and contributes to the establishment and maintenance of aggressive phenotypic characteristics through modulation of several biological processes.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ALK / Analysis / Antibodies / Apoptosis / Biomedical and Life Sciences / Biomedicine / Biotechnology / Cancer / Cancer Research / Cancer stem cell / Carcinoma / CD56 antigen / Cell cycle / Chromosome rearrangements / Development and progression / Disease susceptibility / Endometrial cancer / Endometrial carcinoma / Endometrium / Epithelial-mesenchymal transition / Flow cytometry / Gene expression / Health aspects / Health Promotion and Disease Prevention / Hybridization / Immunoreactivity / Kinases / Lymphoma / Malignancy / Medical colleges / Medicine/Public Health / Mutation / Neuroendocrine differentiation / Non-Hodgkin's lymphomas / Oncology / Phenotypes / Prevention / Protein-tyrosine kinase / Risk factors / RNA / Solid tumors / Stem cells / Surgical Oncology / Synaptophysin / Tumors / Uterine cancer / Women / Womens health