Progression on tumor microenvironment regulations by mechanical forces from Qiyi Zhao Group

Recently, Prof. Qiyi Zhao's group from the Third Affiliated Hospital of Sun Yat-sen University, published the latest original research entitled “Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation” in Nature Communications.

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients’ lesions and atomic force microscopy for surgical samples, Prof. Qiyi Zhao's group reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. In conclusion, the study revealed a role of liquid–liquid phase separation as a signal nexus between niche stiffness and transcriptional activities of a pluripotency factor in CSCs.

Prof. Qiyi Zhao, Prof. Jian-You Liao and Prof. Shicheng Su from Sun Yat-sen University, are the corresponding authors. Xinwei Liu, Yingying Ye, Liling Zhu, Xiaoyun Xiao and Boxuan Zhou from Sun Yat-sen University are co-first authors.

The mechanotransducer TAZ was activated and transported into nucleus by niche mechanical forces. TAZ enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4.

Link to the paper: https://www.nature.com/articles/s41467-023-35856-y