Synthetic Dysmobility Screen Unveils an Integrated STK40-YAP-MAPK System Driving Cell Migration

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Jul 29

PMID 34321207

Citations 5

Authors

Ling-Yea Yu

Ting-Jen Tseng

Hsuan-Chao Lin

Chi-Lin Hsu

Ting-Xuan Lu

Chia-Jung Tsai

Yu-Chiao Lin

I Chu

Chien-Tzu Peng

Hou-Jen Chen

Feng-Chiao Tsai

Affiliations

Soon will be listed here.

Abstract

Integrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a "two-hit" screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced the stability of yes-associated protein (YAP) and subsequently decreased YAP transported into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Together, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration and introduced "synthetic dysmobility" as a novel strategy to collaboratively control cell migration.

Citing Articles

Studying Cellular Focal Adhesion Parameters with Imaging and MATLAB Analysis.

Yu L, Tseng T, Lin H, Hsu C, Lu T, Lin Y Bio Protoc. 2023; 13(21):e4867.

PMID: 37969758 PMC: 10632167. DOI: 10.21769/BioProtoc.4867.

Studying Cell Migration (Random and Wound Healing) Parameters with Imaging and MATLAB Analysis.

Yu L, Lin H, Hsu C, Kao T, Tsai F Bio Protoc. 2023; 13(21):e4871.

PMID: 37969751 PMC: 10632163. DOI: 10.21769/BioProtoc.4871.

Yes-associated protein 1 mediates initial cell survival during lorlatinib treatment through AKT signaling in ROS1-rearranged lung cancer.

Yamazoe M, Ozasa H, Tsuji T, Funazo T, Yoshida H, Hashimoto K Cancer Sci. 2022; 114(2):546-560.

PMID: 36285485 PMC: 9899615. DOI: 10.1111/cas.15622.

Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases.

Ju Y, Dai X, Tang Z, Ming Z, Ni N, Zhu D Bioact Mater. 2022; 14:402-415.

PMID: 35386820 PMC: 8964818. DOI: 10.1016/j.bioactmat.2022.01.028.

Computational methods, databases and tools for synthetic lethality prediction.

Wang J, Zhang Q, Han J, Zhao Y, Zhao C, Yan B Brief Bioinform. 2022; 23(3).

PMID: 35352098 PMC: 9116379. DOI: 10.1093/bib/bbac106.

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