Quoc Thang Pham1,2, Naohide Oue1, Yohei Sekino1,3, Yuji Yamamoto1, Yoshinori Shigematsu1,3, Naoya Sakamoto1, Kazuhiro Sentani1, Naohiro Uraoka1,4, Wataru Yasui1. 1. Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. 2. Department of Pathology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. 3. Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Abstract
OBJECTIVE: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. METHODS: TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). RESULTS: TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. CONCLUSION: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.
OBJECTIVE:Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. METHODS:TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). RESULTS:TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. CONCLUSION: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.
Authors: Marta Cecchi; Antonella Mannini; Andrea Lapucci; Angela Silvano; Matteo Lulli; Cristina Luceri; Mario D'Ambrosio; Alberto Chiarugi; Ali H Eid; Astrid Parenti Journal: Front Pharmacol Date: 2022-06-30 Impact factor: 5.988
Authors: Luis F Somarribas Patterson; Soumya R Mohapatra; Dyah L Dewi; Christiane A Opitz; Ahmed Sadik; Michael Platten; Saskia Trump Journal: Br J Cancer Date: 2019-12-10 Impact factor: 7.640