2. Academic Validation
  3. Tension of plus-end tracking protein Clip170 confers directionality and aggressiveness during breast cancer migration

Tension of plus-end tracking protein Clip170 confers directionality and aggressiveness during breast cancer migration

  • Cell Death Dis. 2022 Oct 8;13(10):856. doi: 10.1038/s41419-022-05306-6.
Yunfeng Hu  # 1 2,  Qiu Xie  # 1 2,  Xiang Wu 1 2 3,  Weizhen Liu 1 2,  DongFang Li 1 2,  Chen Li 1 2,  WangXing Zhao 1 2,  LinLin Chen 1 2,  Zihui Zheng 1 2,  GuangMing Li 4,  Jun Guo 5 6
Affiliations

Affiliations

  • 1 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, P. R. China.
  • 2 Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, P. R. China.
  • 3 Department of Anesthesiology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315040, P. R. China.
  • 4 Department of Anesthesiology, Huaian First People's Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, P. R. China. [email protected].
  • 5 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, P. R. China. [email protected].
  • 6 Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, P. R. China. [email protected].
  • # Contributed equally.
PMID: 36209218 DOI: 10.1038/s41419-022-05306-6
Abstract

The microtubule (MT) plus-end binding protein Clip170 is associated closely with breast Cancer invasion and migration. In this study, Clip170 tension observed by a newly designed cpstFRET tension probe was suggested to be positive related to breast Cancer aggressiveness, which could be regulated by α-tubulin detyrosination-induced MT disassembly. Clip170 phosphorylation induced by Ribosomal protein S6 kinase (RSK) could also increase its tension and promote the conversion of a discrete comet-like Clip-170 distribution into a spotty pattern during Cancer metastasis. Heightened Clip170 tension was correlated with the formation of cortactin-associated filopodia and lamellipodia, and then promoted invasion and metastasis both in vitro and in vivo. Meanwhile, Clip170 tension enhanced at the leading edge in directional migration, accompanying with IQGAP1 subcellular distribution variation. Our work indicates that the malignancy and directionality during breast Cancer migration depend on the magnitude and polarization of Clip170 tension, and we suggest Clip170 tension as a new potential drug target for breast Cancer therapy.

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