Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Anticancer Res. 2021 Dec;41(12):5959-5971. doi: 10.21873/anticanres.15415.
BACKGROUND/AIM: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs).
Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKCλ on trypan blue staining and tumor-sphere formation by ALDH1 cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.
GLO 1, PKCλ, and ALDH1A3 tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1 cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1 cells.
GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.
背景/目的：我们研究了 1 型甘油醛-3-磷酸脱氢酶 (GLO 1) 和蛋白激酶 C (PKCλ) 对醛脱氢酶 1 (ALDH1) 阳性乳腺癌干细胞 (CSC) 的抑制作用。
下载并统计分析了乳腺癌基因组数据集（TCGA，n=593；METABRIC，n=1904）。检测了 GLO 1 和 PKCλ 对三阴性乳腺癌 (TNBC) 和基底样乳腺癌来源的 ALDH1 细胞的台盼蓝染色和肿瘤球形成的影响。
GLO 1、PKCλ 和 ALDH1A3 肿瘤在 I/II/III/IV 期样本中富集，根据受体状态与 HER2 和 TNBC 亚型相关，根据 PAM50 与 HER2 富集和基底样亚型相关。抑制 GLO 1（TLSC702）或 PKCλ（ANF）均可抑制肿瘤球形成并促进 ALDH1 细胞死亡。TLSC702 还能有效抑制 PKCλ 敲除的 ALDH1 细胞的肿瘤球形成并诱导其死亡。
GLO 1 和 PKCλ 对 ALDH1 阳性乳腺癌 CSC 的存活至关重要，可能成为治疗 ALDH1 阳性乳腺癌 CSC 的潜在治疗靶点。
