TANGO1 interacts with NRTN to promote hepatocellular carcinoma progression by regulating the PI3K/AKT/mTOR signaling pathway

被引:7
作者
Man, Jing [1 ,3 ]
Zhou, Wanbiao [1 ,3 ]
Zuo, Shi [1 ,3 ]
Zhao, Xueke [2 ,3 ,4 ]
Wang, Qiang [1 ,3 ]
Ma, Huaxing [1 ,3 ]
Li, Hai-Yang [1 ,3 ,5 ]
机构
[1] Guizhou Med Univ, Affiliated Hosp, Dept Hepatobiliary Surg, Guiyang, Guizhou, Peoples R China
[2] Guizhou Med Univ, Affiliated Hosp, Dept Infect Dis, Guiyang, Guizhou, Peoples R China
[3] Guizhou Med Univ, Dept Clin Med, Guiyang, Guizhou, Peoples R China
[4] Guizhou Med Univ, Affiliated Hosp, Dept Infect Dis, 28 Guiyi St, Guiyang, Guizhou, Peoples R China
[5] Guizhou Med Univ, Affiliated Hosp, Dept Hepatobiliary Surg, 28 Guiyi St, Guiyang, Guizhou, Peoples R China
基金
中国国家自然科学基金;
关键词
TANGO1; MIA3; Hepatocellular carcinoma; NRTN; PI3K; AKT; mTOR signaling pathway; MELANOMA INHIBITORY-ACTIVITY; NEURONAL PLASTICITY; TUMOR-SUPPRESSOR; CANCER; SECRETION; NEURTURIN; PROTEIN; GENES; SITES; CELLS;
D O I
10.1016/j.bcp.2023.115615
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Transport and Golgi organization 1 (TANGO1) also known as MIA3, belongs to the melanoma inhibitory activity gene (MIA) family together with MIA, MIA2 and OTOR; these members play different roles in different tumors, but the mechanism underlying TANGO1s effect on hepatocellular carcinoma (HCC) is unclear. Our study confirmed that TANGO1 is a promoter of HCC, In HCC cells, TANGO1 can promote proliferation, inhibit apoptosis, promote EMT. These changes were reversed after TANGO1 inhibition. We explored the molecular mechanism of TANGO1 and HCC and found that the promoting effect of TANGO1 on HCC related to neurturin (NRTN) and the PI3K/AKT/mTOR signaling pathway based on RNA-seq results. NRTN is not only related to neuronal growth, differentiation and maintenance but is also involved in a variety of tumorigenic processes, and PI3K/AKT/mTOR signaling pathway has been shown to be involved in HCC progression. We verified that TANGO1 interacts with NRTN in HCC cells using endogenous Co-IP and confocal localization, and both promote HCC progression by activating the PI3K/AKT/mTOR signaling pathway. Our results reveal the mechanism by which TANGO1 promotes HCC progression, suggesting that the TANGO1/NRTN axis may be a potential therapeutic target for HCC worthy of further investigation.
引用
收藏
页数:14
相关论文
共 46 条
[1]   Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells [J].
Aherrahrou, Redouane ;
Guo, Liang ;
Nagraj, V. Peter ;
Aguhob, Aaron ;
Hinkle, Jameson ;
Chen, Lisa ;
Yuhl Soh, Joon ;
Lue, Dillon ;
Alencar, Gabriel F. ;
Boltjes, Arjan ;
van der Laan, Sander W. ;
Farber, Emily ;
Fuller, Daniela ;
Anane-Wae, Rita ;
Akingbesote, Ngozi ;
Manichaikul, Ani W. ;
Ma, Lijiang ;
Kaikkonen, Minna U. ;
Bjorkegren, Johan L. M. ;
Onengut-Gumuscu, Suna ;
Pasterkamp, Gerard ;
Miller, Clint L. ;
Owens, Gary K. ;
Finn, Aloke ;
Navab, Mohamad ;
Fogelman, Alan M. ;
Berliner, Judith A. ;
Civelek, Mete .
CIRCULATION RESEARCH, 2020, 127 (12) :1552-1565
[2]   Interactions of TANGO and leukocyte integrin CD11c/CD18 regulate the migration of human monocytes [J].
Arndt, Stephanie ;
Melle, Christian ;
Mondal, Krishna ;
Klein, Gerd ;
von Eggeling, Ferdinand ;
Bosserhoff, Anja-Katrin .
JOURNAL OF LEUKOCYTE BIOLOGY, 2007, 82 (06) :1466-1472
[3]   TANGO is a tumor suppressor of malignant melanoma [J].
Arndt, Stephanie ;
Bosserhoff, Anja K. .
INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (12) :2812-2820
[4]   Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer [J].
Aung, PP ;
Oue, N ;
Mitani, Y ;
Nakayama, H ;
Yoshida, K ;
Noguchi, T ;
Bosserhoff, AK ;
Yasui, W .
ONCOGENE, 2006, 25 (17) :2546-2557
[5]   Characterization and expression pattern of the novel MIA homolog TANGO [J].
Bosserhoff, AK ;
Moser, M ;
Buettner, R .
GENE EXPRESSION PATTERNS, 2004, 4 (04) :473-479
[6]   Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity [J].
Bosserhoff, AK ;
Stoll, R ;
Sleeman, JP ;
Bataille, F ;
Buettner, R ;
Holak, TA .
LABORATORY INVESTIGATION, 2003, 83 (11) :1583-1594
[7]  
Bosserhoff AK, 1997, CANCER RES, V57, P3149
[8]   EMT in cancer [J].
Brabletz, Thomas ;
Kalluri, Raghu ;
Angela Nieto, M. ;
Weinberg, Robert A. .
NATURE REVIEWS CANCER, 2018, 18 (02) :128-+
[9]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[10]   Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives [J].
Corti, Francesca ;
Nichetti, Federico ;
Raimondi, Alessandra ;
Niger, Monica ;
Prinzi, Natalie ;
Torchio, Martina ;
Tamborini, Elena ;
Perrone, Federica ;
Pruneri, Giancarlo ;
Di Bartolomeo, Maria ;
de Braud, Filippo ;
Pusceddu, Sara .
CANCER TREATMENT REVIEWS, 2019, 72 :45-55