Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1.
BACKGROUND
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. However, a previous study demonstrated that LETM1 served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis.


RESULTS
Therefore, we examine the possibility that LETM1 may function to regulate mitochondria and lung tumor growth. In this study, we addressed this question by studying in the effect of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice. To investigate the effects of adenovirus-LETM1 in vitro, we infected with adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by delivering the LETM1 via aerosol through nose-only inhalation system. The effects of LETM1 on lung cancer growth and AMPK related signals were evaluated. Adenovirus-mediated overexpression of LETM1 could induce destruction of mitochondria of lung cancer cells through depleting ATP and AMPK activation. Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell cycle while facilitating apoptosis. Theses results demonstrated that adenovirus-LETM1 suppressed lung cancer cell growth in vitro and in vivo.


CONCLUSIONS
Adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment.
Hwang
Soon-Kyung
SK
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Piao
Longzhen
L
Lim
Hwang-Tae
HT
Minai-Tehrani
Arash
A
Yu
Kyeong-Nam
KN
Ha
Youn-Cheol
YC
Chae
Chan-Hee
CH
Lee
Kee-Ho
KH
Beck
George R
GR
Park
Jongsun
J
Cho
Myung-Haing
MH
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009385:Neoplastic Processes; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C488528:LETM1 protein, human; C000594750:LETM1 protein, mouse; D008565:Membrane Proteins
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