Systematic network-based discovery of a Fam20C inhibitor (FL-1607) with apoptosis modulation in triple-negative breast cancer.
Family with sequence similarity 20, member C (Fam20C) is a physiological Golgi casein kinase that phosphorylates multiple secreted proteins. Recently, it has been reported that Fam20C can be identified as a novel kinase target for therapeutic development. Thus, inhibition of Fam20C will be a potential therapeutic strategy to prevent tumor cell progression and metastasis. In our study, based upon the systems-biology network, molecular modeling and molecular dynamics (MD) simulations, we discovered a novel Fam20C inhibitor (FL-1607) with potent anti-proliferative effects on triple-negative breast cancer (TNBC) cells. Subsequently, we found that this Fam20C inhibitor could induce apoptosis and inhibit cell migration in MDA-MB-468 cells. Together, these findings would provide a new clue to the exploration of more novel Fam20C inhibitors for future TNBC therapy.
Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China. daiyi1004@163.com.
Ziyi
Z
Qin
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Peiqi
P
Wang
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Xinyi
X
Li
State Key Laboratory of Biotherapy & Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. leilei_fu@163.com.
Shouyue
S
Zhang
State Key Laboratory of Biotherapy & Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. leilei_fu@163.com.
Mao
M
Tian
Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou 510632, China. daiyi1004@163.com.
Yi
Y
Dai
State Key Laboratory of Biotherapy & Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. leilei_fu@163.com.
Leilei
L
Fu
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D047389:Casein Kinase I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D063990:Gene Ontology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D058977:Molecular Sequence Annotation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D013329:Structure-Activity Relationship; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D047389:Casein Kinase I; C524449:FAM20C protein, human