RT Journal Article
SR Electronic
T1 High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3299
OP 3312
DO 10.21873/anticanres.15818
VO 42
IS 7
A1 AYAKA OZAKI
A1 HITOMI MOTOMURA
A1 SHOMA TAMORI
A1 CHOTARO ONAGA
A1 YUKA NAGASHIMA
A1 MAHO KOTORI
A1 CHIKA MATSUDA
A1 AKARI MATSUDA
A1 NANAKO MOCHIZUKI
A1 TSUGUMICHI SATO
A1 YASUSHI HARA
A1 KEIKO SATO
A1 YOHEI MIYAGI
A1 YOJI NAGASHIMA
A1 TAKEHISA HANAWA
A1 YOHSUKE HARADA
A1 YUYUN XIONG
A1 KAZUNORI SASAKI
A1 SHIGEO OHNO
A1 KAZUNORI AKIMOTO
YR 2022
UL http://ar.iiarjournals.org/content/42/7/3299.abstract
AB 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.