SEMA4B inhibits growth of non-small cell lung cancer in vitro and in vivo.
We have recently shown that Semaphorin 4B (SEMA4B) inhibits the invasion of non-small cell lung cancer (NSCLC) through PI3K-dependent suppression of MMP9 activation. In the current study, we evaluated whether SEMA4B may also affect the growth of NSCLC. We thus used two human NSCLC lines, A549 and Calu-3, to examine our hypothesis. We found that overexpression of SEMA4B significantly decreased NSCLC cell growth, while SEMA4B inhibition significantly increased NSCLC cell growth, both in vitro and in vivo in an implanted NSCLC model. Adaptation of SEMA4B in NSCLC cells did not alter cell apoptosis, but changed the cell proliferation. Further analyses show that SEMA4B may induce FoxO1 nuclear retention through suppressing PI3K/Akt signaling pathway, which subsequently inhibited cell growth through the direct nuclear target of FoxO1, p21. Our study thus demonstrate a role of SEMA4B in suppressing NSCLC growth, besides its role in inhibiting cell metastasis, and highlights SEMA4B as a promising therapeutic target for NSCLC.
Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Hong
H
Jian
Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Yi
Y
Zhao
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Bin
B
Liu
Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China. Electronic address: shun_lu14@163.com.
Shun
S
Lu
D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D039961:Semaphorins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared; D014183:Transplantation, Heterologous
D050759:Cyclin-Dependent Kinase Inhibitor p21; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D039961:Semaphorins; C000603593:semaphorin 4B, human; D019869:Phosphatidylinositol 3-Kinases
FoxO1; Non-small cell lung cancer (NSCLC); P21; PI3K; SEMA4B