Nodal signaling modulates the expression of Oct-4 via nuclear translocation of β-catenin in lung and prostate cancer cells.
Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation. This increase was attributed to GSK-3β dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Yi-Fei
YF
Qi
Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China.
Long
L
Wu
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Zi-Qian
ZQ
Li
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Meng-Ling
ML
Wu
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Hai-Fang
HF
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Ka-Ying
KY
Chan
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
Lin-Lin
LL
Lu
Department of Pharmacology, School of Pharmaceutical Sciences, Jinan University, Guangzhou 510632, China.
Shao-Hui
SH
Cai
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: whongsh@mail.sysu.edu.cn.
Hong-Sheng
HS
Wang
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: dujun@mail.sysu.edu.cn.
Jun
J
Du
D000072283:A549 Cells; D021581:Active Transport, Cell Nucleus; D030201:Activin Receptors, Type I / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D055457:Nodal Protein / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism*
C495270:CTNNB1 protein, human; C526007:NODAL protein, human; D055457:Nodal Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D051176:beta Catenin; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I
ALK4/7; Nodal; Oct-4; Wnt/β-catenin signaling pathways