title: Feedback regulation of telomerase reverse transcriptase: new insight into the evolving field of telomerase in cancer.
abstract: Telomerase reverse transcriptase (TERT) is the catalytic component of telomerase, especially the rate-limiting determinant of telomerase activity. So far, TERT has been reported to be over-expressed in more than 90% of cancers, thereby playing a critical role in sustained proliferation and survival potentials of various cancer cells. Over the past decade, a comprehensive network of transcription factors has been shown to be involved in the regulation of TERT. Furthermore, accumulating evidence has suggested that TERT could modulate the expression of numerous genes involved in diverse group of cellular processes, including cell cycle regulation and cellular signaling. Therefore, it indicates that TERT is both an effector and a regulator in carcinoma. However, the mechanisms of the interaction between TERT and its target genes are still not fully understood. Thus, it is necessary to consolidate and summarize recent developments of the cross-talk between TERT and related genes in cancer cells or other cells with cancer cell characteristics, and elucidate these relevant mechanisms. In this review, we focus on various signaling pathways and genes that participate in the feedback regulation of TERT and the underlying feedback loop mechanism of TERT, further providing new insights into non-telomeric functions of telomerase and potentially to be used as a novel therapeutic target for cancer.
authors.affiliation: School of Pharmacy, Anhui Medical University, Meishan Road, Hefei, 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), China; Key Laboratory of Antiinflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Wu
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.forename: Yuan-Yao
authors.initials: YY
authors.lastname: Tian
authors.forename: De-Xi
authors.initials: DX
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019098:Telomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C509186:TERT protein, human; D019098:Telomerase
keywords: APC; ATL; BRG1; Brahma-related gene 1; C-terminal extension; COX-2; CSCs; CTE; Cancer; DAT; ECM; EMT; ES; FAK; Feedback loop; Frz; GSK3β; HIF1-α; IKK; IL-6; IκBα; Jab1; Klf; Kruppel-like factor 4; LPS; LRP5/6; MMP-9; Non-telomeric function; PI3K; PTEN; PtdIns3 kinase; RNA interference; RNAi; RNP; RT; RTKs; SCLC; SMARCA4; SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4; T-cell factor-lymphoid enhancer-binding factor; TEN; TERT; TERT RNA-binding; TGF-β; TNF-α; TR; TRAP; TRB; TRF; Tcf-Lef; Telomerase reverse transcriptase (TERT); VEGF; adenomatous polyposis coli; adult T-cell leukemia; bHLHZip; basic helix–loop helix–leucine-zipper; c-Jun activation domain-binding protein-1; cancer stem cells; cyclooxygenase-2; dissociates activities of telomerase; embryonic stem; epithelial-mesenchymal transition; extracellular matrix; focal adhesion kinase; frizzled; glycogen synthase kinase 3β; hypoxia inducible factor 1α; inhibitor of NF-κB; inhibitor of nuclear factor kappa-B kinase; interleukin-6; lipopolysaccharide; low-density lipoprotein receptor-related protein 5/6; matrix metalloproteinase-9; pRb; phosphatase and tensin homologue deleted from chromosome 10; phosphorylation of the retinoblastoma protein; receptor tyrosine kinases; reverse transcriptase; ribonucleoprotein; small cell lung cancer; telomerase RNA; telomerase essential N-terminal; telomerase reverse transcriptase; telomeric repeat amplification protocol; terminal restriction fragment; transforming growth factor-β; tumor necrosis factor-α; vascular endothelial growth factor