ABCB5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | ABCB5 , ABCB5alpha, ABCB5beta, EST422562, ATP binding cassette subfamily B member 5 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 611785 MGI: 1924956 HomoloGene: 83488 GeneCards: ABCB5 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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ATP-binding cassette sub-family B member 5 also known as P-glycoprotein ABCB5 is a plasma membrane-spanning protein that in humans is encoded by the ABCB5 gene. [5] [6] ABCB5 is an ABC transporter and P-glycoprotein family member principally expressed in physiological skin and human malignant melanoma. [7] [8] [9]
ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma, colorectal cancer, and malignant pleural mesothelioma. It is commonly over-expressed on circulating melanoma tumour cells. [10] [11] Furthermore, the ABCB5+ melanoma- initiating cells were demonstrated to express FLT1 ( VEGFR1 ) receptor tyrosine kinase which was functionally required for efficient xenograft tumor formation, as demonstrated by shRNA knockdown experiments. [12]
In colorectal cancer, ABCB5 was shown to act as a mediator of 5-FU patient chemoresistance, and had a further direct role in tumorigenesis shown by shRNA-mediated colorectal cancer cell-line ABCB5 knockdowns that impeded tumorigenesis in human-to-mouse xenografts. [13] It has been shown that in some highly aggressive tumors, such as mesothelioma and melanoma, ABCB5 contributes to multi-drug chemotherapy resistance, and tumor growth, controlling a proinflammatory signaling circuit utilizing TLR4, IL-1β, IL8 and CXCR1 signaling involving reciprocal paracrine interactions between the cancer stem cells and tumor bulk population (in a rheostat manner termed "cancer stem cell rheostasis"). [14] [15] ABCB5 was shown to maintain the slow-cycling melanoma stem cells using this cytokine signaling loop, which became more differentiated upon ABCB5 interference (e.g. WFDC1 melanocyte differentiation marker increased, cancer cells were faster growing in vitro, tumors were more pigmented), or CXCR1 blockade (slow-cycling ABCB5+ cells entered the cell-cycle). [15]
In normal physiology, ABCB5 is a functional marker for adult limbal stem cells of the cornea. ABCB5+ cells could regrow a human cornea on a mouse with limbal stem cell deficiency (LSCD - a blindness disease of the corneal limbus) while ABCB5- cells could not, indicating a therapeutic potential for treating some types of blindness. ABCB5 was further shown to be anti-apoptotic in these adult stem cells. [16]
P-glycoprotein 1 also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.
Cancer stem cells (CSCs) are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.
CD133 antigen, also known as prominin-1, is a glycoprotein that in humans is encoded by the PROM1 gene. It is a member of pentaspan transmembrane glycoproteins, which specifically localize to cellular protrusions. When embedded in the cell membrane, the membrane topology of prominin-1 is such that the N-terminus extends into the extracellular space and the C-terminus resides in the intracellular compartment. The protein consists of five transmembrane segments, with the first and second segments and the third and fourth segments connected by intracellular loops while the second and third as well as fourth and fifth transmembrane segments are connected by extracellular loops. While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.
CD146 also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage. In humans, the CD146 protein is encoded by the MCAM gene.
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CD166 antigen is a 100-105 kD typeI transmembrane glycoprotein that is a member of the immunoglobulin superfamily of proteins. In humans it is encoded by the ALCAM gene. It is also called CD166, MEMD, SC-1/DM-GRASP/BEN in the chicken, and KG-CAM in the rat.
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Homeobox protein Hox-B13 is a protein that in humans is encoded by the HOXB13 gene.
T-box transcription factor 2 Tbx2 is a transcription factor that is encoded by the Tbx2 gene on chromosome 17q21-22 in humans. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. Tbx2 and Tbx3 are the only T-box transcription factors that act as transcriptional repressors rather than transcriptional activators, and are closely related in terms of development and tumorigenesis. This gene plays a significant role in embryonic and fetal development through control of gene expression, and also has implications in various cancers. Tbx2 is associated with numerous signaling pathways, BMP, TGFβ, Wnt, and FGF, which allow for patterning and proliferation during organogenesis in fetal development.
CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1 gene. CDCP1 has also been designated as CD318 and Trask. Alternatively spliced transcript variants encoding distinct isoforms have been reported.
BRCA1 associated protein-1 is a deubiquitinating enzyme that in humans is encoded by the BAP1 gene. BAP1 encodes an 80.4 kDa nuclear-localizing protein with a ubiquitin carboxy-terminal hydrolase (UCH) domain that gives BAP1 its deubiquitinase activity. Recent studies have shown that BAP1 and its fruit fly homolog, Calypso, are members of the polycomb-group proteins (PcG) of highly conserved transcriptional repressors required for long-term silencing of genes that regulate cell fate determination, stem cell pluripotency, and other developmental processes.
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In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.
In molecular biology, the miR-200 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by binding and cleaving mRNAs or inhibiting translation. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141, and miR-429. There is growing evidence to suggest that miR-200 microRNAs are involved in cancer metastasis.
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Gopal Chandra Kundu is an renowned Indian cell and cancer biologist and a Senior Scientist (Scientist-G) at National Centre for Cell Science. He is known for his contributions towards the understanding the mechanism of cancer progression in breast, melanoma and other cancers and development of novel therapeutic targets and target-based therapy in cancers.
In molecular biology mir-301 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.
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Breast cancer is the most prevalent type of cancer among women globally, with 685,000 deaths recorded worldwide in 2020. The most commonly used treatment methods for breast cancer include surgery, radiotherapy and chemotherapy. Some of these treated patients experience disease relapse and metastasis. The aggressive progression and recurrence of this disease has been attributed the presence of a subset of tumor cells known as breast cancer stem cells (BCSCs). These cells possess the abilities of self-renewal and tumor initiation, allowing them to be drivers of metastases and tumor growth. The microenvironment in which these cells reside is filled with residential inflammatory cells that provide the needed signaling cues for BCSC-mediated self-renewal and survival. The production of cytokines allows these cells to escape from the primary tumor and travel through the circulation to distant organs, commencing the process of metastasis. Due to their significant role in driving disease progression, BCSCs represent a new target by which to treat the tumor at the source of metastasis.