Identification of new cancer stem cell markers and signaling pathways in HER‑2‑positive breast cancer by transcriptome sequencing

Abstract

Human epidermal growth factor receptor (HER)-2-positive breast cancer accounts for ~25% of all breast cancer cases, has a high propensity for relapse, metastasis and drug resistance, and is associated with a poor prognosis. Therefore, it is necessary to develop more effective therapeutic targets for the treatment of HER-2-positive breast cancer. CD44+/CD24−/low is currently the most commonly used marker for breast cancer stem cells (CSCs), which are considered the main cause of drug resistance, relapse and metastasis. In the present study, the ratio of CD44+/CD24−/low cells was almost zero in SK-BR-3 cells; however, it was >90% in MDA-MB-231 cells, as determined by flow cytometry. Since SK-BR-3 and MDA-MB-231 cells both exhibit a strong propensity for invasion and migration, it was hypothesized that there may be other markers of CSCs in SK-BR-3 cells. Therefore, transcriptome sequencing was performed for SK-BR-3 and MDA-MB-231 cells. It was observed that several leukocyte differentiation antigens and other CSC markers were significantly more highly expressed in SK-BR-3 cells. Furthermore, the expression of aldehyde dehydrogenase (ALDH)1A3, CD164 and epithelial cell adhesion molecule (EpCAM) was higher in SK-BR-3 cells compared with in other subtypes of breast cell lines, as determined by reverse transcription-polymerase chain reaction and western blot analysis. In addition, the expression levels of ALDH1A3, ALDH3B2 and EpCAM were higher in HER-2-positive breast cancer compared with in paracancerous tissues and other subtypes of breast cancer, as determined by immunohistochemistry. The expression of β-catenin in the Wnt signaling pathway was lower in SK-BR-3 cells compared with in MDA-MB-231 cells, which may be used as a prognostic indicator for breast cancer. These findings may help identify novel CSC markers and therapeutic targets for HER-2-positive breast cancer.

Elevated Ras related GTP binding B (RRAGB) expression predicts poor overall survival and constructs a prognostic nomogram for colon adenocarcinoma

“…Consistent with our results, all of these three signaling pathways had been reported to be markedly related to colon cancer [33][34][35]. As reported by previous articles, Wnt and ERBB signaling pathway played important roles in cancer [36,37]. Yan et al reported that LINC00261 could regulate miR-324-3p and the Wnt signaling pathway to repress colon cancer progression [38].…”

Cancer Stem-Like Phenotype of Mitochondria Dysfunctional Hep3B Hepatocellular Carcinoma Cell Line

“…Surface markers, such as CD133 and CD90, are widely used to identify CSCs [ 23 , 25 , 27 ], but the expression of these surface markers was not observed in Hep3B/ρ 0 cells (data not shown). However, some studies suggest that the classification of CSCs using surface markers is not accurate [ 40 , 41 , 42 ]. Therefore, we focused on the acquisition of superior self-renewal capability in Hep3B/ρ 0 cells regardless of the presence of the markers.…”

Overlapping variants in the blood, tissues and cell lines for patients with intracranial meningiomas are predominant in stem cell-related genes

“…The ALDH3B2 gene encodes a member of the aldehyde dehydrogenase family, a group of isozymes that play a role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. Gene overexpression has been associated with breast cancer stem cells [ 52 ]. The ASPN gene encodes the Asporin protein, which is thought to regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression.…”