B7-H4 facilitates proliferation and metastasis of colorectal carcinoma cell through PI3K/Akt/mTOR signaling pathway. 2020

Chun Li, and Yudong Zhan, and Xuzhe Ma, and Hui Fang, and Xiaodong Gai
Department of Pathology, Beihua University Faculty of Medicine, No. 3999 Binjiang East Road, Jilin, 132013, Jilin, People's Republic of China.

B7-H4 is over-expressed in various tumors and may affect many aspects of cancer biology. Our previous studies have reported that the over-expressed B7-H4 in serum or tumor tissue of colorectal carcinoma (CRC) patients was closely related to CRC progression. However, B7-H4 in cell biological characteristics of CRC is not well studied. Here, we investigate the effect of the B7-H4 on cell proliferation, migration and its expression regulated by PI3K/Akt/mTOR signaling pathway in CRC. Firstly, pSilencer 4.1-B7-H4-shRNA vector was constructed and stable transfection was performed on HT-29 cells. Secondly, cell proliferation, cell cycle, cell apoptosis and cell migration were evaluated after B7-H4 silencing, and the expression of Bcl-2, caspase-3, MMP-2 and MMP-9 was also measured. Finally, the regulation of B7-H4 by PI3K/Akt/mTOR signaling pathway was measured followed by treatment with or without PI3K/Akt and mTOR inhibitor. The results showed that the viability of HT-29 cells was significantly decreased after B7-H4 silencing (P < 0.05). B7-H4 silencing significantly increased the apoptosis rate and caspase-3 protein expression while decreased Bcl-2 protein expression (P all < 0.05). B7-H4 silencing also significantly reduced the migration of HT-29 cells (P < 0.01) and the secretion of MMP-2 or MMP-9 (P all < 0.05). Following treatment with PI3K/Akt and mTOR inhibitor in HT-29 cells, the expression of B7-H4 was significantly downregulated compared with untreated group (P all < 0.05). Our results strongly suggest that B7-H4 may be involved in cell proliferation and migration by PI3K/Akt/mTOR signaling pathway. Therefore, blocking B7-H4 signaling might be a novel treatment strategy for CRC.

UI MeSH Term Description Entries
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015179 Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. Colorectal Cancer,Colorectal Carcinoma,Colorectal Tumors,Neoplasms, Colorectal,Cancer, Colorectal,Cancers, Colorectal,Carcinoma, Colorectal,Carcinomas, Colorectal,Colorectal Cancers,Colorectal Carcinomas,Colorectal Neoplasm,Colorectal Tumor,Neoplasm, Colorectal,Tumor, Colorectal,Tumors, Colorectal
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051057 Proto-Oncogene Proteins c-akt Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells. akt Proto-Oncogene Protein,c-akt Protein,AKT1 Protein Kinase,AKT2 Protein Kinase,AKT3 Protein Kinase,Akt-alpha Protein,Akt-beta Protein,Akt-gamma Protein,Protein Kinase B,Protein Kinase B alpha,Protein Kinase B beta,Protein Kinase B gamma,Protein-Serine-Threonine Kinase (Rac),Proto-Oncogene Protein Akt,Proto-Oncogene Protein RAC,Proto-Oncogene Proteins c-akt1,Proto-Oncogene Proteins c-akt2,Proto-Oncogene Proteins c-akt3,RAC-PK Protein,Rac Protein Kinase,Rac-PK alpha Protein,Rac-PK beta Protein,Related to A and C-Protein,c-akt Proto-Oncogene Protein,Akt alpha Protein,Akt beta Protein,Akt gamma Protein,Akt, Proto-Oncogene Protein,Protein, akt Proto-Oncogene,Protein, c-akt Proto-Oncogene,Proteins c-akt1, Proto-Oncogene,Proteins c-akt2, Proto-Oncogene,Proteins c-akt3, Proto-Oncogene,Proto Oncogene Protein Akt,Proto Oncogene Protein RAC,Proto Oncogene Proteins c akt,Proto Oncogene Proteins c akt1,Proto Oncogene Proteins c akt2,Proto Oncogene Proteins c akt3,Proto-Oncogene Protein, akt,Proto-Oncogene Protein, c-akt,RAC PK Protein,RAC, Proto-Oncogene Protein,Rac PK alpha Protein,Rac PK beta Protein,Related to A and C Protein,akt Proto Oncogene Protein,alpha Protein, Rac-PK,c akt Proto Oncogene Protein,c-akt, Proto-Oncogene Proteins,c-akt1, Proto-Oncogene Proteins,c-akt2, Proto-Oncogene Proteins,c-akt3, Proto-Oncogene Proteins
D058570 TOR Serine-Threonine Kinases A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity. TOR Kinase,TOR Kinases,TOR Serine-Threonine Kinase,Target of Rapamycin Protein,mTOR Serine-Threonine Kinase,mTOR Serine-Threonine Kinases,FK506 Binding Protein 12-Rapamycin Associated Protein 1,FKBP12-Rapamycin Associated Protein,FKBP12-Rapamycin Complex-Associated Protein,Mammalian Target of Rapamycin,Mechanistic Target of Rapamycin Protein,RAFT-1 Protein,Rapamycin Target Protein,Target of Rapamycin Proteins,mTOR Protein,FK506 Binding Protein 12 Rapamycin Associated Protein 1,FKBP12 Rapamycin Associated Protein,FKBP12 Rapamycin Complex Associated Protein,Kinase, TOR,Kinase, TOR Serine-Threonine,Kinase, mTOR Serine-Threonine,Kinases, TOR Serine-Threonine,Kinases, mTOR Serine-Threonine,Protein Target, Rapamycin,Protein, RAFT-1,Protein, mTOR,RAFT 1 Protein,Rapamycin Protein Target,Serine-Threonine Kinase, TOR,Serine-Threonine Kinase, mTOR,Serine-Threonine Kinases, TOR,Serine-Threonine Kinases, mTOR,TOR Serine Threonine Kinase,TOR Serine Threonine Kinases,mTOR Serine Threonine Kinase,mTOR Serine Threonine Kinases

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