TY - JOUR T1 - High Expression of <em>p62</em> and <em>ALDH1A3</em> Is Associated With Poor Prognosis in Luminal B Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 3299 LP - 3312 DO - 10.21873/anticanres.15818 VL - 42 IS - 7 AU - AYAKA OZAKI AU - HITOMI MOTOMURA AU - SHOMA TAMORI AU - CHOTARO ONAGA AU - YUKA NAGASHIMA AU - MAHO KOTORI AU - CHIKA MATSUDA AU - AKARI MATSUDA AU - NANAKO MOCHIZUKI AU - TSUGUMICHI SATO AU - YASUSHI HARA AU - KEIKO SATO AU - YOHEI MIYAGI AU - YOJI NAGASHIMA AU - TAKEHISA HANAWA AU - YOHSUKE HARADA AU - YUYUN XIONG AU - KAZUNORI SASAKI AU - SHIGEO OHNO AU - KAZUNORI AKIMOTO Y1 - 2022/07/01 UR - http://ar.iiarjournals.org/content/42/7/3299.abstract N2 - Background/Aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear. Materials and Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded. p62 Expression was then examined in normal and breast cancer tissues derived from the same patients. Kaplan-Meier and multivariate Cox regression analyses were employed to evaluate disease-specific survival. Next, the effect on cell viability and in vitro tumor-sphere formation of p62 knockdown using targeted small interfering RNA was assessed by using cells with high activity of aldehyde dehydrogenase 1 (ALDH1high). Results: Patients with normal-like, luminal A or luminal B breast cancer with p62high had poor prognosis. Furthermore, patients with p62high ALDH1A3high luminal B type also exhibited poor prognoses. Knockdown of p62 suppressed viability and tumor-sphere formation by ALDH1high cells of the luminal B-type cell lines BT-474 and MDA-MB-361. These results suggest that p62 is essential for cancerous progression of ALDH1-positive luminal B breast CSCs, and contributes to poor prognosis of luminal B breast cancer. Conclusion: p62 is potentially a prognostic marker and therapeutic target for ALDH1-positive luminal B breast CSCs. ER -