OCT4 Expression Enhances Features of Cancer Stem Cells in a Mouse Model of Breast Cancer

Abstract

The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for metastasis and disease recurrence. Therefore, targeting CSCs has the potential to significantly improve outcomes for cancer patients. The OCT4 transcription factor gene is a master gene that plays a key role in the self-renewal and pluripotency of stem cells. In this study, we introduced an OCT4 reporting vector into 4T1 mouse breast cancer cells and sorted OCT4 high and OCT4 low cell populations. We then determined whether OCT4 expression is associated with maintenance and expansion of CSCs. We found that OCT4high 4T1 cells have an increased ability to form tumorsphere and a high expression of stem cell markers such as Sca-1, CD133, CD34, and ALDH1, when compared with OCT4low 4T1 cells. In addition, OCT4high 4T1 cells have greater tumorigenic potential in vivo. These findings suggest that OCT4 expression may be a useful target for stem cell-specific cancer therapy.

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving β-catenin/E-cadherin complex degradation

“…In addition, Oct4 has been implicated in various human cancers and was reported to be associated with tumor progression or bad prognosis (12)(13)(14)(15)(16)(17). The present study demonstrated that the mRNA and protein expression of Oct4 was higher in human lung cancer tissues than that in adjacent normal tissues.…”

Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells

“…108 Indeed, Oct4 is expressed in a subpopulation of breast and ovarian cancer cells that possess self-renewal ability, 109,110 and Oct4 overexpression is sufficient to enhance tumor-propagating cells in a mouse model of breast carcinoma. 111 Beltran et al recently confirmed that the sole transduction of Oct4 in primary human mammary epithelial breast cell preparations from reduction mammoplasty donors was sufficient to generate cell lines possessing tumor-initiating and colonization capacities. Moreover, the Oct4-transduced breast cells displayed a gene signature compatible with that of claudin-low breast carcinomas, which is a molecular subtype of breast cancer that is highly enriched in cancer stem cell-like features.…”

Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

“…Numerous studies have shown that Oct-4 activates transcription via the octamer motif of an AGTCAAAT consensus sequence, and affects mammalian development by regulating the pluripotent potential of stem cells (3)(4)(5)(6)(7). Subsequent studies have demonstrated that Oct-4 is also expressed in a number of types of tumor cells, and that it has potential as a biomarker for the diagnosis and prognosis of malignant tumors (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Further studies have indicated that Oct-4 may be important in cancer cell survival, and that it exerts multiple functions in tumor cells.…”

“…This suggests that Oct-4 functions as a master switch during differentiation, by regulating the pluripotent potential of stem cells, and that it is important during mammalian development. Other studies have demonstrated that Oct-4 is expressed in various types of human tumor, including gastric cancer (8,9), breast cancer (10), non-small cell lung carcinoma (11), glioma (12)(13)(14), esophageal squamous cell carcinoma (15) and certain types of testicular germ cell tumors (16,17). Furthermore, aberrant expression of Oct-4 has been shown to be involved in maintaining self-renewal, and the cancer stem cell-like, and chemoradioresistant properties of lung cancer (18).…”