A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis.
The plant homeodomain (PHD) finger-containing proteins have been implicated in many human diseases including cancer. In this study, we found that PHF14, a newly identified PHD finger protein, is highly expressed in lung cancer. The high expression level of PHF14 was associated with adenocarcinoma and poor survival in lung cancer patients. Knocking down PHF14 suppressed cancer cell growth and carcinogenesis, while over-expressing PHF14 promoted cell proliferation. During cell division, PHF14 directly bound to and co-localized with KIF4A (a nuclear motor protein involved in lung carcinogenesis) to form a functional complex. Similarly to the effect of KIF4A depletion, silencing PHF14 in several cell lines caused cell mitotic defects, prolonged M phase, and inhibited cell proliferation. What's more, these two proteins had a synergistic effect on cell proliferation and were significantly co-overexpressed in lung cancer tissues. Our data provide new insights into the biological significance of PHD finger proteins and imply that PHF14 may be a potential biomarker for lung cancer.
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Lin
L
Zhang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Qin
Q
Huang
Shanghai Lung Tumor Clinical Medical Center, Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.
Jiatao
J
Lou
Institute of Cardiothoracic Surgery, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai, China.
Liangjian
L
Zou
Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Yiguo
Y
Wang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Peng
P
Zhang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Guang
G
Yang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Junyi
J
Zhang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Lan
L
Yu
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Dai
D
Yan
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Chenyi
C
Zhang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Jing
J
Qiao
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Shuting
S
Wang
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.
Sai
S
Wang
Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Yongdong
Y
Xu
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.|School of Life Science and Technology, Shanghai Tech University, Shanghai, China.|CAS Center for Excellence in Molecular Cell Science, SIBCB, SIBS, CAS, Shanghai, China.
Hongbin
H
Ji
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.|Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, CAS, Shanghai, China.|School of Life Science and Technology, Shanghai Tech University, Shanghai, China.
Zhengjun
Z
Chen
Key Laboratory of Systems Biology, Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Science (CAS), Shanghai, China.|Cancer Research Center, Shanghai Xu-Hui Central Hospital, Shanghai Clinical Center, CAS, Shanghai, China.
Zhe
Z
Zhang
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D008938:Mitosis / Q000502:physiology*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C576054:Phf14 protein, mouse; D014157:Transcription Factors; C484228:KIF4A protein, human; D016547:Kinesins
KIF4A; PHF14; biomarker; lung carcinogenesis; mitosis