Theranostics 2019; 9(23):7003-7015. doi:10.7150/thno.35561 This issue Cite

Research Paper

FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer

Alain Mangé1✉*, Etienne Coyaud2*, Caroline Desmetz3, Estelle Laurent2, Benoit Béganton1,4, Peter Coopman1, Brian Raught3, Jérôme Solassol1,4

1. IRCM, INSERM, Univ Montpellier, ICM, Montpellier, France.
2. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
3. BC2M, Univ Montpellier, Montpellier, France
4. CHU Montpellier, Department of Pathology and onco-biology, Montpellier, France.
*A.M., and E. C. contributed equally to this work.

Citation:
Mangé A, Coyaud E, Desmetz C, Laurent E, Béganton B, Coopman P, Raught B, Solassol J. FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics 2019; 9(23):7003-7015. doi:10.7150/thno.35561. https://www.thno.org/v09p7003.htm
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Abstract

Graphic abstract

Purpose: Among the FKBP family members, FKBP4 has been described to have a potential role in tumorigenesis, and as a putative tissue marker. We previously showed that FKBP4, an HSP90-associated co-chaperone, can elicit immune response as a tumor-specific antigen, and are overexpressed in breast cancer.

Experimental design: In this study, we examined how loss of FKBP4 affect breast cancer progression and exploited protein interactomics to gain mechanistic insight into this process.

Results: We found that FKBP4 expression is associated with breast cancer progression and prognosis, especially of ER-negative breast cancer. Furthermore, FKBP4 depletion specifically reduces cell growth and proliferation of triple negative breast cancer cell model and xenograft tumor model. Using specific protein interactome strategy by BirA proximity-dependent biotin identification, we demonstrated that FKBP4 is a novel PI3K-Akt-mTOR proximal interacting protein.

Conclusion: Our results suggest that FKBP4 interacts with PI3K and can enhance Akt activation through PDK1 and mTORC2.

Keywords: FKBP52, FKBP4, BioID, AKT, breast cancer, mTOR


Citation styles

APA
Mangé, A., Coyaud, E., Desmetz, C., Laurent, E., Béganton, B., Coopman, P., Raught, B., Solassol, J. (2019). FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics, 9(23), 7003-7015. https://doi.org/10.7150/thno.35561.

ACS
Mangé, A.; Coyaud, E.; Desmetz, C.; Laurent, E.; Béganton, B.; Coopman, P.; Raught, B.; Solassol, J. FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics 2019, 9 (23), 7003-7015. DOI: 10.7150/thno.35561.

NLM
Mangé A, Coyaud E, Desmetz C, Laurent E, Béganton B, Coopman P, Raught B, Solassol J. FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics 2019; 9(23):7003-7015. doi:10.7150/thno.35561. https://www.thno.org/v09p7003.htm

CSE
Mangé A, Coyaud E, Desmetz C, Laurent E, Béganton B, Coopman P, Raught B, Solassol J. 2019. FKBP4 connects mTORC2 and PI3K to activate the PDK1/Akt-dependent cell proliferation signaling in breast cancer. Theranostics. 9(23):7003-7015.

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