PUBLICATION
TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation
- Authors
- Kim, H.K., Bhattarai, K.R., Junjappa, R.P., Ahn, J.H., Pagire, S.H., Yoo, H.J., Han, J., Lee, D., Kim, K.W., Kim, H.R., Chae, H.J.
- ID
- ZDB-PUB-201002-2
- Date
- 2020
- Source
- Nature communications 11: 4012 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis Regulatory Proteins/antagonists & inhibitors*
- Apoptosis Regulatory Proteins/genetics
- Apoptosis Regulatory Proteins/metabolism
- Calcium/metabolism
- Cell Line, Tumor
- Cell Transformation, Neoplastic/drug effects
- Endoplasmic Reticulum/metabolism
- Humans
- Indenes/pharmacology*
- Mechanistic Target of Rapamycin Complex 2/metabolism*
- Membrane Proteins/antagonists & inhibitors*
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Mice
- Neoplasms/genetics
- Neoplasms/metabolism*
- Neoplasms/pathology
- Protein Binding
- Proto-Oncogene Proteins c-akt/metabolism*
- Ribosomes/metabolism
- Signal Transduction
- Survival Analysis
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 32782388 Full text @ Nat. Commun.
Citation
Kim, H.K., Bhattarai, K.R., Junjappa, R.P., Ahn, J.H., Pagire, S.H., Yoo, H.J., Han, J., Lee, D., Kim, K.W., Kim, H.R., Chae, H.J. (2020) TMBIM6/BI-1 contributes to cancer progression through assembly with mTORC2 and AKT activation. Nature communications. 11:4012.
Abstract
Transmembrane B cell lymphoma 2-associated X protein inhibitor motif-containing (TMBIM) 6, a Ca2+ channel-like protein, is highly up-regulated in several cancer types. Here, we show that TMBIM6 is closely associated with survival in patients with cervical, breast, lung, and prostate cancer. TMBIM6 deletion or knockdown suppresses primary tumor growth. Further, mTORC2 activation is up-regulated by TMBIM6 and stimulates glycolysis, protein synthesis, and the expression of lipid synthesis genes and glycosylated proteins. Moreover, ER-leaky Ca2+ from TMBIM6, a unique characteristic, is shown to affect mTORC2 assembly and its association with ribosomes. In addition, we identify that the BIA compound, a potentialTMBIM6 antagonist, prevents TMBIM6 binding to mTORC2, decreases mTORC2 activity, and also regulates TMBIM6-leaky Ca2+, further suppressing tumor formation and progression in cancer xenograft models. This previously unknown signaling cascade in which mTORC2 activity is enhanced via the interaction with TMBIM6 provides potential therapeutic targets for various malignancies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping