Downregulation of TfR1 promotes progression of colorectal cancer via the JAK/STAT pathway

• Main Authors: Cui C, Cheng X, Yan L, Ding H, Guan X, Zhang W, Tian X, Hao C
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: Cancer Management and Research
• Subjects: Colorectal cancer; transferrin receptor 1; tumor progression; JAK/STAT pathway.
• Online Access: https://www.dovepress.com/downregulation-of-tfr1-promotes-progression-of-colorectal-cancer-via-t-peer-reviewed-article-CMAR

Can Cui,1 Xiaojing Cheng,2 Liang Yan,1 Huirong Ding,3 Xiaoya Guan,1 Wenlong Zhang,4 Xiuyun Tian,1 Chunyi Hao11Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Carcinoma Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaBackground: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies. The incidence of CRC has been rapidly increasing in China. Transferrin receptor 1 (TfR1) is a key regulator of cellular iron homeostasis. Several studies have demonstrated TfR1 overexpression in a variety of human tumors, but the association between TfR1 and CRC remains unclear.Methods: TfR1 expression was evaluated in six CRC cell lines and tumor tissues. A total of 201 CRC patients were included for immunohistochemistry and 19 pairs of frozen tissues were used for real-time PCR. Cell proliferation, cell cycle, cell migration and invasion, and in vivo carcinogenesis were tested after downregulation of TfR1 by lentivirus. Protein microarray and Western blot analyses were used to explore the underlying mechanisms of TfR1 in CRC.Results: TfR1 expression was higher in CRC tissues than in normal tissues (57.2% vs 22.9%, P＜0.001). TfR1 expression was obviously higher in CRC tissues with well differentiation (P＝0.008), no lymph node metastasis (P＝0.002), no distant metastasis (P＝0.006), no vascular invasion (P＜0.001) and early TNM stage (P＝0.013). CRC patients with TfR1-positive expression had a better survival than those with TfR1-negative expression (P＝0.044). Downregulation of TfR1 expression inhibited cell proliferation, promoted cells from G1 phase to S phase and facilitated cell migration and invasion. Knockdown of TfR1 also suppressed tumor growth in BALB/C-nu mice. Protein microarray and Western blot analyses showed that the Janus protein tyrosine kinase/signal transducer and activator of transcription pathway was activated along with downregulation of TfR1 expression.Conclusion: Though TfR1 was overexpressed in colorectal cancer tissues, there was evidence that downregulation of TfR1 could promote cancer progression.Keywords: colorectal cancer, transferrin receptor 1, tumor progression, JAK/STAT pathway