OBJECTIVETo gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs).

DATA SOURCESThe data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "SOX2," "cancer," "tumor" or "CSCs."

STUDY SELECTIONArticles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.

RESULTSSOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRY-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet.

CONCLUSIONSHere, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology of neoplasia, such as Wnt/β-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, PI3K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

Animals ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Neoplastic Stem Cells ; pathology

Aldehyde dehydrogenase 1 (ALDH1, ALDH1A1 or RALDH1), an enzyme responsible for the oxidation of intracellular aldehydes, was shown to have a function in the early differentiation of stem cells. Its activity shows promising potential as a universal marker for the identification and isolation of normal stem cells and cancer stem cells from multiple sources in a variety of tissue types. Herein, we review the available data reporting the utilization of ALDH1 activity as a means to identify and isolate normal stem cells and cancer stem cells (CSCs), and the potential diagnostic and therapeutic implications, with a special focus on the mammary gland and breast cancer. The research opportunity in this area of interest is emphasized.
Animals ; Biomarkers ; metabolism ; Biomarkers, Tumor ; metabolism ; Humans ; Isoenzymes ; metabolism ; Neoplastic Stem Cells ; metabolism ; Retinal Dehydrogenase ; metabolism ; Stem Cells ; metabolism

As a highly conserved RNA binding protein, Lin28 is a specific post-transcriptional inhibitor of let-7 biogenesis and can inhibit the let-7 processing and synthesis. Lin28 is involved in the stem cell proliferation and promote the rapid growth of embryonic stem cells. Lin28 plays an important role in the formation of tumor stem cells. Overexpression of Lin28 promotes the tumor cell proliferation and is associated with advanced human cancers. Lin28 can promote tissue repair.
Cell Proliferation ; Embryonic Stem Cells ; metabolism ; Humans ; MicroRNAs ; metabolism ; Neoplasms ; metabolism ; Neoplastic Stem Cells ; metabolism ; RNA-Binding Proteins ; metabolism

Tumor cells have unique energy metabolism phenomena, namely high glucose absorption, aerobic glycolysis and high lactic acid production, which are characterized by down-regulation of related proteins involved in oxidative metabolism in tumor cells, and up-regulation of glucose transporters and monocarboxylate transporters. Studies have shown that drugs that target tumor cell glucose metabolism have the ability to selectively kill tumor cells, bringing new hope for tumor treatment. Tumor stem cells are considered to be the root cause of tumor recurrence, metastasis and poor prognosis, and their energy metabolism characteristics have not yet been agreed. Studies have shown that reversing the energy metabolism of tumor stem cells can increase their chemosensitivity. This article reviews recent studies on tumor and tumor stem cell glucose metabolism and the opportunities and challenges of tumor treatment through targeting glucose metabolism, which might provide new ideas and opportunities for clinical tumor therapy.
Energy Metabolism ; Glucose ; metabolism ; Glycolysis ; Humans ; Lactic Acid ; metabolism ; Neoplasms ; metabolism ; Neoplastic Stem Cells ; metabolism

Cancer stem cells represent a subpopulation of cells within tumor mass, endowed with self-renewal, survival, proliferation, and tumorigenic capacity. These cell populations are potentially associated with cancer prognosis. However, these cells do not play a part in isolation; instead, they are dependent on a variety of signals from their microenvironments. Cancer stem cells have two microenvironment niches: the first one is perivascular niche and the second is hypoxic regions where tumor stem cells locate. Bidirectional signal transduction is found between cancer stem cells and cancer stem cell niches. As a cancer stem cell-specific surface marker, CD133 plays a role in key molecular signaling pathways and high levels of drug-or radiation-resistance. Other molecules closely related to cancer stem cell signaling pathways include Wnt and Hh, which are also associated with cancer drug resistance. Further understanding the molecular mechanisms of pathological basis of cancer stem cells will facilitate the development of new therapeutic targets and new strategies for eradicating cancers. This paper summarizes the molecular mechanisms, and the possibilities and limitations of therapies targeting cancer stem cell.
Humans ; Neoplasms ; metabolism ; therapy ; Neoplastic Stem Cells ; metabolism ; Signal Transduction ; Stem Cell Niche ; Tumor Microenvironment

CD47, also known as integrin-associated protein (IAP), is an immunoglobulin-like protein. It can inhibit the phagocytosis of macrophages through binding with signal-regulatory protein alpha chain of inhibitory receptor on macrophage (SIRPα). The expression of CD47 on normal hematopoietic stem cells (HSCs) is useful for maintaining the stability of HSCs in body, but the high expression of CD47 existed on leukemia stem cell (LSCs) of AML patients which can reduce the macrophage-induced phagocytosis to LSCs and decrease the clearance of innate immune system of organism to LSCs. In this article, the expression and function of CD47 on HSCs and LSCs as well as the role of CD47 in the prognosis and target therapy of AML are reviewed.
CD47 Antigen ; metabolism ; Humans ; Leukemia ; metabolism ; Macrophages ; metabolism ; Neoplastic Stem Cells ; metabolism ; Phagocytosis

Cancer stem cells (CSCs), a subpopulation of cancer cells with ability of initiating tumorigenesis, exist in many kinds of tumors including breast cancer. Cancer stem cells contribute to treatment resistance and relapse. Conventional treatments only kill differentiated cancer cells, but spare CSCs. Combining conventional treatments with therapeutic drugs targeting to CSCs will eradicate cancer cells more efficiently. Studying the molecular mechanisms of CSCs regulation is essential for developing new therapeutic strategies. Growing evidences showed CSCs are regulated by non-coding RNA (ncRNA) including microRNAs and long non-coding RNAs (lncRNAs), and histone-modifiers, such as let-7, miR-93, miR-100, HOTAIR, Bmi-1 and EZH2. Herein we review the roles of microRNAs, lncRNAs and histone-modifiers especially Polycomb family proteins in regulating breast cancer stem cells (BCSCs).
Breast Neoplasms ; genetics ; metabolism ; pathology ; Histones ; metabolism ; Humans ; Neoplastic Stem Cells ; metabolism ; RNA, Untranslated ; genetics ; metabolism

MicroRNAs (miRNAs) are small non-coding RNAs that regulate messenger RNAs at the post-transcriptional level. They play an important role in the control of cell physiological functions, and their alterations have been related to cancer, where they can function as oncogenes or tumor suppressor genes. Recently, they have emerged as key regulators of "stemness", collaborating in the maintenance of pluripotency, control of self-renewal, and differen-tiation of stem cells. The miRNA pathway has been shown to be crucial in embryonic development and in embryonic stem (ES) cells, as shown by Dicer knockout analysis. Specific patterns of miRNAs have been reported to be expressed only in ES cells and in early phases of embryonic development. Moreover, many cancers present small populations of cells with stem cell characteristics, called cancer stem cells (CSCs). CSCs are responsible for relapse and treatment failure in many cancer patients, and the comparative analysis of expression patterns between ES cells and tumors can lead to the identification of a miRNA signature to define CSCs. Most of the key miRNAs identified to date in ES cells have been shown to play a role in tumor diagnosis or prognosis, and may well prove to be essential in cancer therapy in the foreseeable future.
Embryonic Stem Cells/cytology/*metabolism ; Humans ; MicroRNAs/genetics/*metabolism ; Models, Biological ; Neoplastic Stem Cells/cytology/*metabolism ; Signal Transduction/genetics/*physiology

Although the notion that cancer is a disease caused by genetic and epigenetic alterations is now widely accepted, perhaps more emphasis has been given to the fact that cancer is a genetic disease. It should be noted that in the post-genome sequencing project period of the 21st century, the underlined phenomenon nevertheless could not be discarded towards the complete control of cancer disaster as the whole strategy, and in depth investigation of the factors associated with tumorigenesis is required for achieving it. Otto Warburg has won a Nobel Prize in 1931 for the discovery of tumor bioenergetics, which is now commonly used as the basis of positron emission tomography (PET), a highly sensitive noninvasive technique used in cancer diagnosis. Furthermore, the importance of the cancer stem cell (CSC) hypothesis in therapy-related resistance and metastasis has been recognized during the past 2 decades. Accumulating evidence suggests that tumor bioenergetics plays a critical role in CSC regulation; this finding has opened up a new era of cancer medicine, which goes beyond cancer genomics.
Animals ; *Energy Metabolism/genetics/physiology ; *Genomics ; Humans ; Neoplasms/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism