Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases

Joechle K, Jumaa H, Thriene K, Hellerbrand C, Kulemann B, Fichtner-Feigl S, Lang SA, Guenzle J (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Frontiers in Cell and Developmental Biology Frontiers Media

Book Volume: 9

Article Number: 785979

DOI: 10.3389/fcell.2021.785979

Abstract

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027—a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

Authors with CRIS profile

Claus Hellerbrand Professur für Biochemie und Molekulare Pathobiologie

Involved external institutions

Universitätsklinikum Aachen (UKA) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Joechle, K., Jumaa, H., Thriene, K., Hellerbrand, C., Kulemann, B., Fichtner-Feigl, S.,... Guenzle, J. (2022). Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases. Frontiers in Cell and Developmental Biology, 9. https://dx.doi.org/10.3389/fcell.2021.785979

MLA:

Joechle, Katharina, et al. "Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases." Frontiers in Cell and Developmental Biology 9 (2022).

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