Cancer stem cells and HER2 positive breast cancer: The story so far

Shah, Deep; Osipo, Clodia

doi:10.1016/j.gendis.2016.02.002

Cited by 49 publications

(47 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tyrosine-phosphorylation of ErbB2 leads to the activation of the PI3K-AKT, Ras-Raf-MEK-ERK, and JAK-STAT signalling pathways 1–5,27–30,32 . We therefore examined the effects of nectin-4 on the activation of these signalling pathways.…”

Section: Resultsmentioning

confidence: 99%

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Kedashiro

Mizutani

Takai

2019

Sci Rep

View full text Add to dashboard Cite

Nectin-4 cell adhesion molecule and ErbB2 tyrosine kinase receptor are upregulated in many cancers, including breast cancer, and promote cancer cell proliferation and metastasis. Using human breast cancer cell lines T47D and SUM190-PT, in which both nectin-4 and ErbB2 were upregulated, we showed here that nectin-4 cis-interacted with ErB2 and enhanced its dimerization and activation, followed by the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. The third immunoglobulin-like domain of nectin-4 cis-interacted with domain IV of ErbB2. This region differs from the trastuzumab-interacting region but is included in the trastuzumab-resistant splice variants of ErbB2, p95-ErbB2 and ErbB2ΔEx16. Nectin-4 also cis-interacted with these trastuzumab-resistant splice variants and enhanced the activation of the phosphoinositide 3-kinase-AKT signalling pathway for DNA synthesis. In addition, nectin-4 enhanced the activation of the p95-ErbB2-induced JAK-STAT3 signalling pathway, but not the ErbB2- or ErbB2ΔEx16-induced JAK-STAT3 signalling pathway. These results indicate that nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants and enhances the activation of these receptors and downstream signalling pathways in a novel mechanism.

show abstract

Section: Resultsmentioning

confidence: 99%

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Kedashiro

Mizutani

Takai

2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In an in vitro tumorigenic assay, knocking down ESE-1 significantly inhibited tumorsphere formation, revealing that ESE-1 contributes to the maintenance of tumor initiating cells (Figure 8 ). Previous reports have established that the HER2/PI3K/Akt signaling axis is critical to proliferation and sustenance of tumor initiating cells [ 34 , 50 , 51 ]. In addition, the NF-KB, IL-8-CXCR1/2, JAK-STAT axes have been implicated in promoting self-renewal and differentiation of HER2 + breast cancer stem cells [ 34 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports have established that the HER2/PI3K/Akt signaling axis is critical to proliferation and sustenance of tumor initiating cells [ 34 , 50 , 51 ]. In addition, the NF-KB, IL-8-CXCR1/2, JAK-STAT axes have been implicated in promoting self-renewal and differentiation of HER2 + breast cancer stem cells [ 34 , 50 , 51 ]. As mentioned above, we found that expression of some of these key genes are altered upon ESE-1 knockdown ( Supplementary Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

ESE-1/ELF3 mRNA expression associates with poor survival outcomes in HER2+ breast cancer patients and is critical for tumorigenesis in HER2+ breast cancer cells

Kar

Gutierrez‐Hartmann

2017

Oncotarget

View full text Add to dashboard Cite

ESE-1/Elf3 and HER2 appear to establish a positive feedback regulatory loop, but the precise role of ESE-1 in HER2+ breast tumorigenesis remains unknown. Analyzing public repositories, we found that luminal B and HER2 subtype patients with high ESE-1 mRNA levels displayed worse relapse free survival. We stably knocked down ESE-1 in HER2+ luminal B BT474 cells and HER2 subtype SKBR3 cells, which resulted in decreased cell proliferation, colony formation, and anchorage-independent growth in vitro. Stable ESE-1 knockdown inhibited HER2-dependent signaling in BT474 cells and inhibited mTOR activation in SKBR3 cells, but reduced Akt signaling in both cell types. Expression of a constitutively-active Myr-Akt partially rescued the anti-proliferative effect of ESE-1 knockdown in both cell lines. Furthermore, ESE-1 knockdown inhibited cyclin D1, resulting in a G1 delay in both cell lines. Finally, ESE-1 knockdown completely inhibited BT474 cell xenograft tumors in NOD/SCID female mice, which correlated with reduced in vitro tumorsphere formation. Taken together, these results reveal the ESE-1 controls transformation via distinct upstream signaling mechanisms in SKBR3 and BT474 cells, which ultimately impinge on Akt and cyclin D1 in both cell types to regulate cell proliferation. Particularly significant is that ESE-1 controls tumorigenesis and is associated with worse clinical outcomes in HER2 breast cancer.

show abstract

“…Globally, breast cancer is one of the most common cancers in women that can be treated with lumpectomy, mastectomy, radiation therapy, chemotherapy, and so on [1–3]. Defining the characteristics of breast cancer is important for classifying its subtypes, understanding the disease prognosis, and determining a suitable therapy.…”

mentioning

confidence: 99%

“…Defining the characteristics of breast cancer is important for classifying its subtypes, understanding the disease prognosis, and determining a suitable therapy. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 are the known prognostic and predictive markers for breast cancer [1–3]. According to immunohistochemical and gene expression studies on ER, PR, HER2, and Ki67, human breast cancers are classified into the following subtypes: luminal A‐like (ER+/PR+/HER2−/low Ki67), luminal B/HER2‐negative‐like (ER+/PR+−/HER2−/high Ki67), luminal B/ HER2‐positive‐like (ER+/PR+−/HER2+), HER2‐positive (ER−/PR−/HER2+), and triple‐negative (ER−/PR−/HER2−) [1–3].…”

mentioning

confidence: 99%

rBC2LCN lectin as a potential probe of early‐stage HER2‐positive breast carcinoma

et al. 2020

View full text Add to dashboard Cite

The recombinant N‐terminal domain of BC2L‐C lectin (rBC2LCN) is useful for detecting not only human pluripotent stem cells but also some cancers. However, the cancer types and stages that can be detected by rBC2LCN remain unclear. In this study, we identified the human breast carcinoma subtypes and stages that can be detected by rBC2LCN. Compared with rBC2LCN‐negative breast carcinoma cell lines, the rBC2LCN‐positive cells expressed higher levels of human epidermal growth factor receptor 2 (HER2) and epithelial marker genes. Importantly, rBC2LCN histochemical staining of human breast carcinoma tissues demonstrated the utility of rBC2LCN in detecting breast carcinoma types that express HER2 and have not spread much in the early phase of growth. We conclude that rBC2LCN may have potential as a detection probe and a drug delivery vehicle to identify and treat early‐stage HER2‐positive breast carcinoma.

show abstract

Cancer stem cells and HER2 positive breast cancer: The story so far

Cited by 49 publications

References 58 publications

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

Nectin-4 cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, enhancing their activation and DNA synthesis

ESE-1/ELF3 mRNA expression associates with poor survival outcomes in HER2+ breast cancer patients and is critical for tumorigenesis in HER2+ breast cancer cells

rBC2LCN lectin as a potential probe of early‐stage HER2‐positive breast carcinoma

Contact Info

Product

Resources

About