@article{14080,
  abstract     = {Extracellular signal-regulated kinase (ERK) has been recognized as a critical regulator in various physiological and pathological processes. Extensive research has elucidated the signaling mechanisms governing ERK activation via biochemical regulations with upstream molecules, particularly receptor tyrosine kinases (RTKs). However, recent advances have highlighted the role of mechanical forces in activating the RTK–ERK signaling pathways, thereby opening new avenues of research into mechanochemical interplay in multicellular tissues. Here, we review the force-induced ERK activation in cells and propose possible mechanosensing mechanisms underlying the mechanoresponsive ERK activation. We conclude that mechanical forces are not merely passive factors shaping cells and tissues but also active regulators of cellular signaling pathways controlling collective cell behaviors.},
  author       = {Hirashima, Tsuyoshi and Hino, Naoya and Aoki, Kazuhiro and Matsuda, Michiyuki},
  issn         = {1879-0410},
  journal      = {Current Opinion in Cell Biology},
  number       = {10},
  publisher    = {Elsevier},
  title        = {{Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation}},
  doi          = {10.1016/j.ceb.2023.102217},
  volume       = {84},
  year         = {2023},
}

@article{12238,
  abstract     = {Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.},
  author       = {Hino, Naoya and Matsuda, Kimiya and Jikko, Yuya and Maryu, Gembu and Sakai, Katsuya and Imamura, Ryu and Tsukiji, Shinya and Aoki, Kazuhiro and Terai, Kenta and Hirashima, Tsuyoshi and Trepat, Xavier and Matsuda, Michiyuki},
  issn         = {1534-5807},
  journal      = {Developmental Cell},
  keywords     = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
  number       = {19},
  pages        = {2290--2304.e7},
  publisher    = {Elsevier},
  title        = {{A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration}},
  doi          = {10.1016/j.devcel.2022.09.003},
  volume       = {57},
  year         = {2022},
}