title: Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death.
abstract: Death-associated protein 1 (DAP1) is a member of the DAP family and has been implicated in the regulation of cell growth and death including that of cancer cells. However, the roles of DAP1 in clinical cancer and in the regulation of colorectal cancer cells are largely unknown. The present study investigated the expression profile of DAP1 in human colorectal cancer and the impact of DAP1 on apoptosis and the cellular response to 5-FU. Human colorectal cancer specimens (n=94) and human colorectal cancer cell lines HRT18 and HT115 were used. DAP1 transcript and protein were evaluated using quantitative transcript analysis and immunohistochemistry. DAP1-knockdown cells were generated using anti-DAP1 transgene. The results revealed that human colorectal cancer tissues had lower levels of DAP1 when compared with the normal tissues. The reduced levels were associated with higher Dukes' stage and lymph node metastasis. Patients with low DAP1 expression had a markedly reduced survival. Loss of DAP1 in colorectal cancer cells resulted in a gain in cellular migration and loss of their sensitivity of apoptosis to chemotherapeutic agent, 5-FU. DAP1 was found to be correlated with disease progression and long-term survival of the colorectal patients. DAP1 is also a pivotal regulator of the growth and apoptosis and cellular response to chemotherapy agents.
authors.affiliation: Cardiff University-Peking University School of Oncology Joint Institute, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Jia
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Toms
authors.forename: Mansel Leigh
authors.initials: ML
authors.lastname: Davies
authors.forename: Fiona
authors.initials: F
authors.lastname: Ruge
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.forename: Rachel
authors.initials: R
authors.lastname: Hargest
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D012333:RNA, Messenger / Q000096:biosynthesis; D016896:Treatment Outcome; D014945:Wound Healing / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C091572:DAP protein, human; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D005472:Fluorouracil