Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer

被引：24

作者：

Weidner, Philip ^{[1
]}

Soehn, Michaela ^{[1
]}

Gutting, Tobias ^{[1
]}

Friedrich, Teresa ^{[1
]}

Gaiser, Timo ^{[2
]}

Magdeburg, Julia ^{[3
]}

Kienle, Peter ^{[3
]}

Ruh, Hermelindis ^{[4
]}

Hopf, Carsten ^{[4
]}

Behrens, Hans-Michael ^{[5
]}

Roecken, Christoph ^{[5
]}

Hanoch, Tamar ^{[6
]}

Seger, Rony ^{[6
]}

Ebert, Matthias P. A. ^{[1
]}

Burgermeister, Elke ^{[1
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Med 2, D-68167 Mannheim, Germany

[2] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Inst Pathol, D-68167 Mannheim, Germany

[3] Heidelberg Univ, Med Fac Mannheim, Univ Med Mannheim, Dept Surg, D-68167 Mannheim, Germany

[4] Mannheim Univ Appl Sci, ABIMAS Res Ctr, D-68163 Mannheim, Germany

[5] Univ Kiel, Inst Pathol, D-24105 Kiel, Germany

[6] Weizmann Inst Sci, Dept Biol Regulat, I-7610001 Rehovot, Israel

来源：

ONCOTARGET | 2016年 / 7卷 / 31期

关键词：

colorectal cancer; insulin; MTMR7; phosphatase; myotubularin; GASTRIC-CANCER; METAANALYSIS; PROGRESSION; RECURRENCE; CAVEOLIN-1; EXPRESSION; MUTATIONS; AUTOPHAGY; GENOMICS; FAMILY;

D O I：

10.18632/oncotarget.10466

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth factor receptor signaling. However, the function of myotubularin-related protein 7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated with increasing tumor grade (G), size (T) and stage (UICC) in patients with colorectal cancer (CRC) (n=1786). The presence of MTMR7 in the stroma correlated with poor prognosis, whereas MTMR7 expression in the tumor was not predictive for patients' survival. Insulin reduced MTMR7 protein levels in human CRC cell lines, and CRC patients with type 2 diabetes mellitus (T2DM) or loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) had an increased risk for MTMR7 loss. Mechanistically, MTMR7 lowered PIPs and inhibited insulin-mediated AKT-ERK1/2 signaling and proliferation in human CRC cell lines. MTMR7 provides a novel link between growth factor signaling and cancer, and may thus constitute a potential marker or drug target for human CRC.

引用

页码：50490 / 50506

页数：17

共 50 条

[21] Deficiency of myotubularin-related protein 14 influences body weight, metabolism, and inflammation in an age-dependent manner
Yin Lv
Lu Xue
Congli Cai
Qing-Hua Liu
Jinhua Shen
Cell & Bioscience, 5
[22] Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve
Previtali, SC
Zerega, B
Sherman, DL
Brophy, PJ
Dina, G
King, RHM
Salih, MM
Feltri, L
Quattrini, A
Ravazzolo, R
Wrabetz, L
Monaco, AP
Bolino, A
HUMAN MOLECULAR GENETICS, 2003, 12 (14) : 1713 - 1723
[23] Deficiency of myotubularin-related protein 14 influences body weight, metabolism, and inflammation in an age-dependent manner
Lv, Yin
Xue, Lu
Cai, Congli
Liu, Qing-Hua
Shen, Jinhua
CELL AND BIOSCIENCE, 2015, 5
[24] Receptor mediated endocytosis 8 is a novel PI(3)P binding protein regulated by myotubularin-related 2
Xhabija, Besa
Taylor, Gregory S.
Fujibayashi, Akemi
Sekiguchi, Kiyotoshi
Vacratsis, Panayiotis O.
FEBS LETTERS, 2011, 585 (12): : 1722 - 1728
[25] Phosphatidylinositol-3 phosphatase myotubularin-related protein 6 negatively regulates CD4 T cells
Srivastava, Shekhar
Ko, Kyung
Choudhury, Papiya
Li, Zhai
Johnson, Amanda K.
Nadkarni, Vivek
Unutmaz, Derya
Coetzee, William A.
Skolnik, Edward Y.
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (15) : 5595 - 5602
[26] Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8
Zou, Jun
Zhang, Chunfen
Marjanovic, Jasna
Kisseleva, Marina V.
Majerus, Philip W.
Wilson, Monita P.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (24) : 9539 - 9544
[27] Human myotubularin-related protein 9 regulates ER-to-Golgi trafficking and modulates WNT3A secretion
Doubravska, Lenka
Dostal, Vojtech
Knop, Filip
Libusova, Lenka
Macurkova, Marie
EXPERIMENTAL CELL RESEARCH, 2020, 386 (01)
[28] Expression analysis in the peripheral nerve of the myotubularin-related 2 protein phosphatase, mutated in CMT4B1
Previtali, SC
Zerega, B
Sherman, DL
Brophy, PJ
Dina, G
King, RHM
Salih, MM
Feltri, L
Quattrini, A
Wrabetz, A
Monaco, AP
Bolino, A
GLIA, 2003, : 66 - 66
[29] Myotubularin-related-protein-7 inhibits mutant (G12V) K-RAS by direct interaction
Weidner, Philip
Saar, Daniel
Soehn, Michaela
Schroeder, Torsten
Yu, Yanxiong
Zoellner, Frank G.
Ponelies, Norbert
Zhou, Xiaobo
Zwicky, Andre
Rohrbacher, Florian N.
Pattabiraman, Vijaya R.
Tanriver, Matthias
Bauer, Alexander
Ahmed, Hazem
Ametamey, Simon M.
Riffel, Philipp
Seger, Rony
Bode, Jeffrey W.
Wade, Rebecca C.
Ebert, Matthias P. A.
Kragelund, Birthe B.
Burgermeister, Elke
CANCER LETTERS, 2024, 588
[30] Characterization of an adapter subunit to a phosphatidylinositol (3)P 3-phosphatase: Identification of a myotubularin-related protein lacking catalytic activity
Nandurkar, HH
Caldwell, KK
Whisstock, JC
Layton, MJ
Gaudet, EA
Norris, FA
Majerus, PW
Mitchell, CA
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) : 9499 - 9504

← 1 2 3 4 5 →