Guosheng Lyu1, Peng Su2, Xiaohe Hao1, Shiming Chen2, Shuai Ren1, Zixiao Zhao1, Yaoqin Gong1, Qiao Liu1, Changshun Shao3. 1. Key Laboratory of Experimental Teratology, Ministry of Education, Department of Molecular Medicine and Genetics, School of Basic Medical Sciences, Shandong University, Jinan 250012, China. 2. Department of Pathology, Qilu Hospital of Shandong University, Jinan 250012, China. 3. State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou 215123, China.
Abstract
Objective: RECQL4 (a member of the RECQ helicase family) upregulation has been reported to be associated with tumor progression in several malignancies. However, whether RECQL4 sustains esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we determined the functional role for RECQL4 in ESCC progression. Methods: RECQL4 expression in clinical samples of ESCC was examined by immunohistochemistry. Cell proliferation, cellular senescence, the epithelial-mesenchymal transition (EMT), DNA damage, and reactive oxygen species in ESCC cell lines with RECQL4 depletion or overexpression were analyzed. The levels of proteins involved in the DNA damage response (DDR), cell cycle progression, survival, and the EMT were determined by Western blot analyses. Results: RECQL4 was highly expressed in tumor tissues when compared to adjacent non-tumor tissues in ESCC (P < 0.001) and positively correlated with poor differentiation (P = 0.011), enhanced invasion (P = 0.033), and metastasis (P = 0.048). RECQL4 was positively associated with proliferation and migration in ESCC cells. Depletion of RECQL4 also inhibited growth of tumor xenografts in vivo. RECQL4 depletion induced G0/G1 phase arrest and cellular senescence. Importantly, the levels of DNA damage and reactive oxygen species were increased when RECQL4 was depleted. DDR, as measured by the activation of ATM, ATR, CHK1, and CHK2, was impaired. RECQL4 was also shown to promote the activation of AKT, ERK, and NF-kB in ESCC cells. Conclusions: The results indicated that RECQL4 was highly expressed in ESCC and played critical roles in the regulation of DDR, redox homeostasis, and cell survival. Copyright:
Objective: RECQL4 (a member of the RECQ helicase family) upregulation has been reported to be associated with tumor progression in several malignancies. However, whether RECQL4 sustains esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we determined the functional role for RECQL4 in ESCC progression. Methods: RECQL4 expression in clinical samples of ESCC was examined by immunohistochemistry. Cell proliferation, cellular senescence, the epithelial-mesenchymal transition (EMT), DNA damage, and reactive oxygen species in ESCC cell lines with RECQL4 depletion or overexpression were analyzed. The levels of proteins involved in the DNA damage response (DDR), cell cycle progression, survival, and the EMT were determined by Western blot analyses. Results: RECQL4 was highly expressed in tumor tissues when compared to adjacent non-tumor tissues in ESCC (P < 0.001) and positively correlated with poor differentiation (P = 0.011), enhanced invasion (P = 0.033), and metastasis (P = 0.048). RECQL4 was positively associated with proliferation and migration in ESCC cells. Depletion of RECQL4 also inhibited growth of tumor xenografts in vivo. RECQL4 depletion induced G0/G1 phase arrest and cellular senescence. Importantly, the levels of DNA damage and reactive oxygen species were increased when RECQL4 was depleted. DDR, as measured by the activation of ATM, ATR, CHK1, and CHK2, was impaired. RECQL4 was also shown to promote the activation of AKT, ERK, and NF-kB in ESCC cells. Conclusions: The results indicated that RECQL4 was highly expressed in ESCC and played critical roles in the regulation of DDR, redox homeostasis, and cell survival. Copyright:
Authors: Shepherd H Schurman; Mohammad Hedayati; ZhengMing Wang; Dharmendra K Singh; Elzbieta Speina; Yongqing Zhang; Kevin Becker; Margaret Macris; Patrick Sung; David M Wilson; Deborah L Croteau; Vilhelm A Bohr Journal: Hum Mol Genet Date: 2009-06-29 Impact factor: 6.150
Authors: Victoria Valinluck Lao; Piri Welcsh; Yanxin Luo; Kelly T Carter; Slavomir Dzieciatkowski; Suzanne Dintzis; Jane Meza; Nora E Sarvetnick; Raymond J Monnat; Lawrence A Loeb; William M Grady Journal: Transl Oncol Date: 2013-08-01 Impact factor: 4.243
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