Int J Biol Sci 2019; 15(11):2448-2460. doi:10.7150/ijbs.37241 This issue

Research Paper

Rictor ablation in BMSCs inhibits bone metastasis of TM40D cells by attenuating osteolytic destruction and CAF formation

Zibo Liu*, Hui Wang*, Jialing He, Xiaoqin Yuan, Weiwei Sun

Department of Anatomy, Histology and Embryology, Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China
*These authors contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Liu Z, Wang H, He J, Yuan X, Sun W. Rictor ablation in BMSCs inhibits bone metastasis of TM40D cells by attenuating osteolytic destruction and CAF formation. Int J Biol Sci 2019; 15(11):2448-2460. doi:10.7150/ijbs.37241. Available from

File import instruction


Graphic abstract

The mTOR complex 2 (mTORC2) is recognized as a promising target for breast cancer treatment. As mTORC2-specific inhibitors do not yet exist, studies into the role of mTORC2 in cancer are performed by deleting Rictor or by RNAi-mediated Rictor silencing. The purpose of this study was to explore the effects of Rictor ablation in bone mesenchymal stromal cells (BMSCs) on bone metastasis of breast cancer. First, female mice with the genotype of Prx1-Cre;Rictorf/f (hereafter RiCKO) or Rictorf/f (as control) were injected intratibially with cells of the breast cancer cell line (TM40D) at 4 months of age. Three weeks later, osteolytic bone destruction was detected in metastatic legs by X-ray and micro-CT. We found that Rictor ablation in BMSCs inhibited TM40D-induced osteolytic bone destruction and resulted in greater bone volume maintenance in vivo. Lower CTX-I serum level, a decreased number of TRAP+ osteoclasts and lower Cathepsin-K expression observed at the tumor-bone interface indicated that osteoclastogenesis was inhibited in RiCKO mice. Additionally, co-culture experiments confirmed that Rictor deletion in BMSCs diminished osteoclast differentiation partly via down regulation of RANKL expression. Furthermore, Rictor deficiency was found to reduce the transition of BMSCs to CAFs coupled with decreased secretion of cytokines (IL-6, RANKL, TGFβ), which resulted in lower chemotaxis and less proliferation in TM40D cells. These results suggest that Rictor ablation in BMSCs plays dual roles in breast cancer bone metastasis: (1) repression of osteolytic bone destruction; (2) inhibition of tumor growth.

Keywords: BMSCs, mTOR complex 2, breast cancer bone metastasis, osteolytic bone destruction, CAFs