Open AccessSynthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration
Author(s) -
Yu Liu,
Ting-Jen Tseng,
Hsuan-Chao Lin,
Chi-Lin Hsu,
Ting-Xuan Lu,
ChungJung Tsai,
Yu-Chiao Lin,
Isabel Chu,
Chien-Tzu Peng,
Hou-Jen Chen,
Feng-Chiao Tsai
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abg2106
Subject(s) - mapk/erk pathway , microbiology and biotechnology , cell migration , focal adhesion , motility , protein kinase a , gene knockdown , cell growth , kinase , cell , chemistry , biology , signal transduction , biochemistry , apoptosis
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.