title: Rhomboid domain containing 1 promotes colorectal cancer growth through activation of the EGFR signalling pathway.
abstract: Rhomboid proteins perform a wide range of important functions in a variety of organisms. Recent studies have revealed that rhomboid proteins are involved in human cancer progression; however, the underlying molecular mechanism remains largely unclear. Here we show that RHBDD1, a rhomboid intramembrane serine protease, is highly expressed and closely associated with survival in patients with colorectal cancer. We observe that inactivation of RHBDD1 decreases tumor cell growth. Further studies show that RHBDD1 interacts with proTGFα and induces the ADAM-independent cleavage and secretion of proTGFα. The secreted TGFα further triggers the activation of the EGFR/Raf/MEK/ERK signalling pathway. Finally, the positive correlation of RHBDD1 expression with the EGFR/Raf/MEK/ERK signalling pathway is further corroborated in a murine model of colitis-associated colorectal cancer. These findings provide evidence of a growth-promoting role for RHBDD1 in colorectal cancer and may aid the development of tumor biomarkers or antitumor therapeutics.
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Wei
authors: W
authors: Song
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Wenjie
authors: W
authors: Liu
authors: Department of Abdominal Surgical Oncology, Cancer Hospital &Institute, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors: Hong
authors: H
authors: Zhao
authors: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Shangze
authors: S
authors: Li
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Xin
authors: X
authors: Guan
authors: Department of Pathology, Cancer Hospital &Institute, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors: Jianming
authors: J
authors: Ying
authors: Department of Abdominal Surgical Oncology, Cancer Hospital &Institute, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors: Yefan
authors: Y
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Fei
authors: F
authors: Miao
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Mengmeng
authors: M
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Xiaoxia
authors: X
authors: Ren
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Xiaolu
authors: X
authors: Li
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Fan
authors: F
authors: Wu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Yuechao
authors: Y
authors: Zhao
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Yuanyuan
authors: Y
authors: Tian
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
authors: Wenming
authors: W
authors: Wu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Jun
authors: J
authors: Fu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Junbo
authors: J
authors: Liang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Wei
authors: W
authors: Wu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Changzheng
authors: C
authors: Liu
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Jia
authors: J
authors: Yu
authors: National Research Institute for Family Planning, WHO Collaboration Center of Human Reproduction, Beijing 100081, China.
authors: Shudong
authors: S
authors: Zong
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Shiying
authors: S
authors: Miao
authors: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Xiaodong
authors: X
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors: Linfang
authors: L
authors: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced; D015179:Colorectal Neoplasms / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010957:Plasmids; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D066246:ErbB Receptors; C534711:RHBDD1 protein, human; D012697:Serine Endopeptidases