Mechanistic studies on NOK oncogene related cancer signaling and metabolism
China (IFMSA-China) - Peking Union Medical College, Beijing
Yin Yang
Li Liu
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
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Type of Research Project
- Basic science
What is the background of the project?
Human genomic studies indicate that there are limited receptor protein tyrosine kinase (RPTK) molecules in human genome. To date, out of over 518 known protein kinases in human genome, only 90 of them belong to protein tyrosine kinases (PTKs), while 58 out of 90 PTKs are receptor protein tyrosine kinases (RTKs) in which 19 RTK families have been documented. The novel oncogene with kinase-domain (NOK) represents the latest RPTK family being uncovered. NOK and serine/threonine/tyrosine kinase 1 (STYK1) were independently isolated from human amygdala tissue and human fetal brain cDNA library, respectively. The sequences of NOK and STYK1 are all identical except the amino acid residue 203 at which NOK is proline (P) while STYK1 has leucine (L). Interestingly, this single amino acid substitution markedly reduces the transformation potential of STYK1 in a kinase independent manner. NOK has been shown to be a strong oncogene to induce tumorigenesis and metastasis in animals. NOK activates mutiple mitogenic signaling pathways such as Ras/MAPK, PI3K/Akt and STATs that play critical roles during NOK mediated carcinogenesis.
What is the aim of the project?
Elucidating the cellular pathways or key targets responsible for the complicated interplay among novel oncogene with kinase-domain (NOK) oncogene mediated replication stress, NOK mediated DNA damage response and NOK induced cancer formation.
What techniques and methods are used?
Tissue culture, western blotting, reverse transcription-polymerase chain reaction (RT-PCR), cell proliferation analysis such as 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Cell Counting Kit-8 (CCK8), flow cytometric analysis, cancer cell invasion and migration analysis, colony assay.
What is the role of the student?
- The tasks of the student will be performed on his/her own
What are the tasks expected to be accomplished by the student?
A small project will be specially designed for this student as he/she enters this lab. The main tasks that the student will perform include: 1) using transient transfection and stable cell systems to confirm our previous main observations in novel oncogene with kinase-domain (NOK) mediated metastasis; 2) using mutagenesis approach (we have established these mutant stable cells) to evaluate the critical role(s) that these amino acid residues of NOK may play during NOK mediated metastasis; 3) to elucidate the signaling pathways indispensable for NOK mediated metastasis.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The lab will provide some technical trainings before the initiation of the project. A routine talk about the project will be set between tutor and the student every week. The lab encourages the student to ask any question that they may confront when they conduct the research. The students will actively involved in the weekly group meeting that he/she can give talks.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a presentation
- The student will prepare a scientific report
- The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Tissue culture, western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR).
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Students in biomedical fields
- Wei-Ye Shi; Xiao Yang; Bo Huang; Wen-Hong Shen; Li Liu*. NOK oncogene mediated metabolic and energetic process undergoes Warburg effect with impaired mitochondrial oxidative phosphorylation. Front Biosci (Landmark Ed); 2017;
- Sheng-Qi Hou and Li Liu*. NOK mediated mitogenic signaling is altered by P203L and V395I mutations. Front Biosci (Landmark Ed); 2015; 20:1179-89.
- Li Liu*; Xin-Zi Yu; Tie-Shi Li; Lian-Xia Song; Pei-La Chen; Ying-Hua Li; Shi-Dong Wang; Yue Chen; Yong-Ming Ren; Shu-Ping Zhang; Zhi-Jie Chang; and Xin-Yuan Fu*. 2004. A novel protein tyrosine kinase NOK that shares homology with PDGF/FGF receptors; induces tumorigenesis and metastasis in nude mice. Cancer Res.; 64 (10): 3491-3499.