Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer

H. Kamino; Y. Nakamura; M. Tsuneki; H. Sano; Y. Miyamoto; N. Kitamura; M. Futamura; Y. Kanai; H. Taniguchi; D. Shida; Y. Kanemitsu; Y. Moriya; K. Yoshida; H. Arakawa; M. Zheng; K. B. Turton; F. Zhu; Y. Li; K. M. Grindle; D. S. Annis; L. Lu; A. C. Drennan; D. J. Tweardy; U. Bharadwaj; D. F. Mosher; L. Rui

doi:10.1038/oncsis.2015.43

Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer

H. Kamino, Y. Nakamura, M. Tsuneki, H. Sano, Y. Miyamoto, N. Kitamura, M. Futamura, Y. Kanai, H. Taniguchi, D. Shida, Y. Kanemitsu, Y. Moriya, K. Yoshida, H. Arakawa, M. Zheng, K. B. Turton, F. Zhu, Y. Li, K. M. Grindle, D. S. AnnisL. Lu, A. C. Drennan, D. J. Tweardy, U. Bharadwaj, D. F. Mosher, L. Rui

Infectious Diseases, Infection Control, and Employee Health

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.

Original language	English (US)
Pages (from-to)	e181
Journal	Oncogenesis
Volume	5
DOIs	https://doi.org/10.1038/oncsis.2015.43
State	Published - Jan 4 2016

ASJC Scopus subject areas

Molecular Biology
Cancer Research

Access to Document

10.1038/oncsis.2015.43

Cite this

Kamino, H., Nakamura, Y., Tsuneki, M., Sano, H., Miyamoto, Y., Kitamura, N., Futamura, M., Kanai, Y., Taniguchi, H., Shida, D., Kanemitsu, Y., Moriya, Y., Yoshida, K., Arakawa, H., Zheng, M., Turton, K. B., Zhu, F., Li, Y., Grindle, K. M., ... Rui, L. (2016). Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer. Oncogenesis, 5, e181. https://doi.org/10.1038/oncsis.2015.43

Kamino, H, Nakamura, Y, Tsuneki, M, Sano, H, Miyamoto, Y, Kitamura, N, Futamura, M, Kanai, Y, Taniguchi, H, Shida, D, Kanemitsu, Y, Moriya, Y, Yoshida, K, Arakawa, H, Zheng, M, Turton, KB, Zhu, F, Li, Y, Grindle, KM, Annis, DS, Lu, L, Drennan, AC, Tweardy, DJ , Bharadwaj, U, Mosher, DF & Rui, L 2016, 'Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer', Oncogenesis, vol. 5, pp. e181. https://doi.org/10.1038/oncsis.2015.43

@article{bf5ae40fceeb49ddb254fec0d9748472,

title = "Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer",

abstract = "Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.",

author = "H. Kamino and Y. Nakamura and M. Tsuneki and H. Sano and Y. Miyamoto and N. Kitamura and M. Futamura and Y. Kanai and H. Taniguchi and D. Shida and Y. Kanemitsu and Y. Moriya and K. Yoshida and H. Arakawa and M. Zheng and Turton, {K. B.} and F. Zhu and Y. Li and Grindle, {K. M.} and Annis, {D. S.} and L. Lu and Drennan, {A. C.} and Tweardy, {D. J.} and U. Bharadwaj and Mosher, {D. F.} and L. Rui",

year = "2016",

month = jan,

day = "4",

doi = "10.1038/oncsis.2015.43",

language = "English (US)",

volume = "5",

pages = "e181",

journal = "Oncogenesis",

issn = "2157-9024",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer

AU - Kamino, H.

AU - Nakamura, Y.

AU - Tsuneki, M.

AU - Sano, H.

AU - Miyamoto, Y.

AU - Kitamura, N.

AU - Futamura, M.

AU - Kanai, Y.

AU - Taniguchi, H.

AU - Shida, D.

AU - Kanemitsu, Y.

AU - Moriya, Y.

AU - Yoshida, K.

AU - Arakawa, H.

AU - Zheng, M.

AU - Turton, K. B.

AU - Zhu, F.

AU - Li, Y.

AU - Grindle, K. M.

AU - Annis, D. S.

AU - Lu, L.

AU - Drennan, A. C.

AU - Tweardy, D. J.

AU - Bharadwaj, U.

AU - Mosher, D. F.

AU - Rui, L.

PY - 2016/1/4

Y1 - 2016/1/4

N2 - Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.

AB - Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. BNIP3 and NIX are critical mediators for the Mieap-regulated mitochondrial quality control. Mieap suppresses murine intestinal tumor via its mitochondrial quality control function. To explore the role of the Mieap-regulated mitochondria quality control function in colorectal cancer patients, we examined the statuses of p53, Mieap, BNIP3 and NIX in 57 primary colorectal cancer tissues. Promoter methylation of the Mieap and BNIP3 genes was found in 9% and 47% of colorectal cancer cases, respectively, whereas p53 mutation was found in more than 50% of colorectal cancer tissues lacking methylation of the Mieap and BNIP3 promoters, implying that the p53/Mieap/BNIP3-regulated mitochondria quality control pathway is inactivated in more than 70% of colorectal cancer patients. In LS174T colorectal cancer cells, hypoxia activated the Mieap-regulated mitochondria quality control function. Knockdown of p53, Mieap or BNIP3 in LS174T cells severely impaired the hypoxia-activated function, leading to the accumulation of unhealthy mitochondria and increase of mitochondrial reactive oxygen species generation. The mitochondrial reactive oxygen species generated by unhealthy mitochondria in the p53/Mieap/BNIP3-deficient cells remarkably enhanced cancer cell migration and invasion under hypoxic condition. These results suggest that the Mieap-regulated mitochondria quality control has a critical role in colorectal cancer suppression in the in vivo hypoxic tumor microenvironment.

UR - http://www.scopus.com/inward/record.url?scp=84953869926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953869926&partnerID=8YFLogxK

U2 - 10.1038/oncsis.2015.43

DO - 10.1038/oncsis.2015.43

M3 - Article

C2 - 26727575

AN - SCOPUS:84953869926

SN - 2157-9024

VL - 5

SP - e181

JO - Oncogenesis

JF - Oncogenesis

ER -

Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this