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Human telomerase reverse transcriptase (hTERT) promotes cancer invasion by modulating cathepsin D via early growth response (EGR)-1

 Young-Jin Park  ;  Eun Kyoung Kim  ;  Jung Yoon Bae  ;  Sook Moon  ;  Jin Kim 
 Cancer Letters, Vol.370(2) : 222-231, 2016 
Journal Title
 Cancer Letters 
Issue Date
Animals ; Cathepsin D/physiology* ; Cell Line, Tumor ; Cell Movement ; Early Growth Response Protein 1/physiology* ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mouth Neoplasms/pathology* ; Neoplasm Invasiveness ; Telomerase/physiology*
Cathepsin D ; Early growth response (EGR)-1 ; Human telomerase reverse transcriptase (hTERT) ; Invasion ; Oral squamous cell carcinoma (OSCC)
Human telomerase reverse transcriptase (hTERT) contributes to tumor progression as well as maintaining telomere length, however, the mechanism by which hTERT promotes invasiveness is not yet completely understood. This study aims to unravel the precise mechanism through which hTERT promotes cancer invasion. We established an hTERT-overexpressed immortalized cell line (IHOK/hTERT). In orthotopic xenograft models, IHOK/hTERT harbors higher tumorigenicity than IHOK/Control. IHOK/hTERT showed much higher migration and invasion activities compared to IHOK/Control. IHOK/hTERT co-cultured with fibroblasts displayed increased invasion compared to IHOK/hTERT without fibroblasts. We screened for genes that play an important role in intermodulation between cancer cells and fibroblasts using a microarray and identified fibroblast activation protein (FAP). hTERT knockdown showed decreased expression of FAP and early growth response (EGR)-1, one of the transcriptional regulators of FAP in IHOK/hTERT and oral cancer cell line YD10B. Furthermore, EGR-1 knockdown in IHOK/hTERT and YD10B showed reduced invasion and reduced cathepsin D expression compared to Control-siRNA cells. Taken together, this study provides evidence that hTERT overexpression is responsible for the upregulation of the cysteine protease cathepsin D by regulating EGR-1 to activate invasiveness in cancer progression.
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5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
김진(Kim, Jin)
문숙(Moon, Sook)
박영진(Park, Young Jin)
배정윤(Bae, Jung Yoon) ORCID logo https://orcid.org/0000-0001-8342-6987
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