Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms

被引：72

作者：

Deng, M. ^{[1
,2
,3
,4
]}

Zhang, W. ^{[1
]}

Tang, H. ^{[1
,2
]}

Ye, Q. ^{[1
]}

Liao, Q. ^{[1
,2
]}

Zhou, Y. ^{[1
]}

Wu, M. ^{[1
]}

Xiong, W. ^{[1
]}

Zheng, Y. ^{[1
]}

Guo, X. ^{[1
]}

Qin, Z. ^{[1
]}

He, W. ^{[1
]}

Zhou, M. ^{[1
]}

Xiang, J. ^{[1
]}

Li, X. ^{[1
]}

Ma, J. ^{[1
]}

Li, G. ^{[1
]}

机构：

[1] Cent S Univ, Key Lab Carcinogenesis & Canc Invas, Hunan Key Lab Nonresolving Inflammat & Canc, Key Lab Carcinogenesis,Minist Hlth,Minist Educ,Ca, Changsha 410078, Hunan, Peoples R China

[2] Univ South China, Canc Res Inst, Hengyang, Peoples R China

[3] Guangzhou Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Canc Hosp, Guangzhou, Guangdong, Peoples R China

来源：

ONCOGENE | 2013年 / 32卷 / 36期

关键词：

nasopharyngeal carcinoma; LTF; AKT; PDK1; keratin; 18; 14-3-3; LACTOFERRIN INHIBITS GROWTH; SIMPLE EPITHELIAL KERATINS; CYCLIN-DEPENDENT KINASES; INITIATED COLON-TUMOR; 14-3-3; PROTEINS; BOVINE LACTOFERRIN; DOWN-REGULATION; EXPRESSION; CANCER; PHOSPHORYLATION;

D O I：

10.1038/onc.2012.434

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

LTF (lactotransferrin, also known as lactoferrin) is a key component of innate immune defense. It has recently been found to have anti-tumor and anti-metastatic activity in different cancers. We previously reported LTF to be the most significantly downregulated gene in nasopharyngeal carcinoma (NPC) specimens relative to normal nasopharyngeal epithelial tissues, and it was also negatively associated with the progression and metastasis of NPC. However, the mechanism underlying this remains unclear. In the current study, we revealed that LTF can suppress 3-phosphoinositide-dependent protein kinase 1 expression via the mitogen-activated protein kinase/c-Jun pathway and thus repress AKT signaling. We also showed that LTF interacts with keratin 18 (K18) and so blocks the formation of the K18-14-3-3 complex, leading to downregulation of K18-mediated AKT activation. Thus, LTF suppresses AKT signaling by two separate mechanisms, leading to inhibition of NPC tumorigenesis. This is the first report on the tumor suppressive effects of LTF through repression of AKT signaling in NPC. It suggests that both LTF and AKT signaling merit further study in the field of NPC research.

引用

页码：4273 / 4283

页数：11

共 45 条

[1] Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].