Cancer Stem Cell Oct-4 Research Articles

The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review.

Recently, evidences show that cancer stem cells (CSCs) are a type of cancer cell group with self-renewal and play a huge role in tumor recurrence, metastasis, and drug resistance. Finding new treatment directions and targets for cancer prognosis and reducing mortality has become a top priority. OCT4, as a transcription factor, participates in maintaining the stem characteristics of CSCs, but the mechanism of OCT4 is often overlooked. In this review, we try to illustrate the mechanism by which OCT4 plays a role in CSCs from the perspective of genetic modification of OCT4, non-coding RNA, complexes and signaling pathways associated with OCT4. Our ultimate goal is to provide new targets for cancer treatment to prolong the survival of cancer patients.

Retinoic acid increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma.

Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma, and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma.

Abstract 260: Apigenin nanoparticle suppresses sphere formation in CD133+/ALDH1high prostate cancer stem cells through downregulation of stem cell markers

Abstract The recurrence of prostate cancer after definitive treatment(s) is thought to be due to the potential of rare cancer stem cells (CSCs) to withstand therapy and initiate tumor formation. CSCs are a subpopulation of cancer cells capable of self-renewal and plastic adaptation mediating tumorigenesis, metastasis, and therapy resistance. CSCs are associated with cancer progression and clinical outcome in cancer patients. In the present study, we isolated CSCs from various human prostate cancer 22Rv1, DU145 and PC-3 cells by applying selection of cluster of differentiation 133 cell surface marker and high ALDH1 activity (CD133+/ALDH1high). Next we aimed to identify CD133+/ALDH1high CSCs isolated from human prostate cancer cells and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the CSC population continued to grow in the three-dimensional multicellular spheroids. Differentiation investigated with stem cell-related genomic characteristics exhibited significant increase in genes viz. CD44, Nanog, β-catenin, c-Myc, SOX2 and Oct4 in CSCs at the message level. In further studies we determine the effect of natural plant flavone apigenin on CSC population. Apigenin is abundantly present in common fruits and vegetables and possess remarkable anticancer, anti-angiogenic and anti-metastatic properties. Apigenin loaded polyethylene glycol nanoparticles (Ap-NP) was characterized for particle size, morphology, zeta potential, drug release and encapsulation. Cellular entry and intracellular localization of Ap-NP were assessed by transmission electron microscopy. Treatment of CD133+/ALDH1high CSCs with Ap-NP inhibited cell viability and sphere formation at higher extent in time dependent manner, compared to the non-CSCs counterparts. Furthermore, Ap-NP exposure resulted in the downregulation of Nanog, β-catenin, c-Myc, SOX2 and Oct4 in the CSCs. Taken together, our study demonstrate overexpression of potential CSC markers and the ability to target these CSCs by the use of non-toxic agent apigenin killing this rare population that may lead to the total abolition of tumor recurrence and/or metastasis. Citation Format: Rajnee Kanwal, Sanjeev Shukla, Agata A. Exner, Andreas G. Tzakos, Sanjay Gupta. Apigenin nanoparticle suppresses sphere formation in CD133+/ALDH1high prostate cancer stem cells through downregulation of stem cell markers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 260.

Research progress of Oct-4 in cancer stem cells

Stem cell (SC) is a class of initial cells with potential self renewal and differentiation ability. Under certain conditions, it can proliferate and differentiate into various functional cells. Nucleoprotein Oct-4, Nanog and Sox2 are three major transcription factors, which play central roles in maintaining the pluripotent characteristics and inhibiting SC differentiation. Cancer stem cell(CSC) theory supposed that there is also existing SC-CSC possessing potential self renewal and differentiation abilities in tumor tissues. It is the SC properties of CSC that result in tumor's invasive growth, metastasis and resistance to treatment. Therefore, looking for CSC and determining their markers become an important direction for cancer research. And the introduction of Oct-4, Nanog and Sox2 into CSC research field is undoubtedly the most exciting forefront. Key words: Oct-4; Cancer stem cell

Single-cell clones of liver cancer stem cells have the potential of differentiating into different types of tumor cells

Cancer stem cells (CSCs) are believed to be a promising target for cancer therapy because these cells are responsible for tumor development, maintenance and chemotherapy resistance. Finding out the critical factors regulating CSC fate is the key for target therapy of CSCs. Just as normal stem cells are regulated by their microenvironment (niche), CSCs are also regulated by cells in the tumor microenvironment. However, whether various tumor microenvironments can induce CSCs to differentiate into different cancer cells is not clear. Here, we show that single-cell-cloned CSCs, accidentally obtained from a human liver cancer microvascular endothelial cells, express classic stem cell markers, genes associated with self-renewal and pluripotent factors and possess colony-forming ability in vitro and the ability of serial transplantation in vivo. The single-cell-cloned CSCs treated with the different tumor cell/tissue-derived conditioned culture medium, which is a mimic of carcinoma microenvironment, could differentiate into corresponding tumor cells and express specific markers of the respective type of tumor cells at the gene, protein and cell levels, respectively. Interestingly, this multilineage differentiation potential of single-cell-cloned liver CSCs sharply declined after the specific knockdown of octamer-binding transcription factor 4 (Oct4) alone, even though they were under the same induction conditions (carcinoma microenvironments). These data support the hypothesis that single-cell-cloned liver CSCs have the potential of differentiating into different types of tumor cells, and the tumor microenvironment does play a crucial role in deciding differentiation directions. Simultaneously, Oct4 in CSCs is indispensable in this process. These factors are promising targets for liver CSC-specific therapy.