TY - JOUR
T1 - Ha-RasV12-Induced Multilayer Cellular Aggregates Is Mediated by Rac1 Activation Rather Than YAP Activation
AU - Wu, Li Ying
AU - Han, Chia Lin
AU - Lin, Hsi Hui
AU - Tang, Ming Jer
N1 - Funding Information:
This work was financially supported by the International Center for Wound Repair and Regeneration at National Cheng Kung University from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, and by the grant of the Ministry of Science and Technology (MOST 107-3017-F-006-002, MOST 108-3017-F-006-002, and MOST 109-2634-F-006-021 to MJT).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5
Y1 - 2022/5
N2 - We demonstrate that Ha-RasV12 overexpression induces the nuclear translocation of Hippo effector Yes-associated protein (YAP) in MDCK cells via the hippo-independent pathway at the confluent stage. Ha-RasV12 overexpression leads to the downregulation of Caveolin-1 (Cav1) and the disruption of junction integrity. It has been shown that the disruption of actin belt integrity causes YAP nuclear translocation in epithelial cells at high density. Therefore, we hypothesized that Ha-RasV12-decreased Cav1 leads to the disruption of cell junction integrity, which subsequently facilitates YAP nuclear retention. We revealed that Ha-RasV12 downregulated Cav1 through the ERK pathway. Furthermore, the distribution and expression of Cav1 mediated the cell junction integrity and YAP nuclear localization. This suggests that the downregulation of Cav1 induced by Ha-RasV12 disrupted the cell junction integrity and promoted YAP nuclear translocation. We further indicated the consequence of Ha-RasV12-induced YAP activation. Surprisingly, the activation of YAP is not required for Ha-RasV12-induced multilayer cellular aggregates. Instead, Ha-RasV12 triggered the ERK-Rac pathway to promote cellular aggregate formation. Moreover, the overexpression of constitutively active Rac is sufficient to trigger cellular aggregation in MDCK cells at the confluent stage. This highlights that Rac activity is essential for cellular aggregates.
AB - We demonstrate that Ha-RasV12 overexpression induces the nuclear translocation of Hippo effector Yes-associated protein (YAP) in MDCK cells via the hippo-independent pathway at the confluent stage. Ha-RasV12 overexpression leads to the downregulation of Caveolin-1 (Cav1) and the disruption of junction integrity. It has been shown that the disruption of actin belt integrity causes YAP nuclear translocation in epithelial cells at high density. Therefore, we hypothesized that Ha-RasV12-decreased Cav1 leads to the disruption of cell junction integrity, which subsequently facilitates YAP nuclear retention. We revealed that Ha-RasV12 downregulated Cav1 through the ERK pathway. Furthermore, the distribution and expression of Cav1 mediated the cell junction integrity and YAP nuclear localization. This suggests that the downregulation of Cav1 induced by Ha-RasV12 disrupted the cell junction integrity and promoted YAP nuclear translocation. We further indicated the consequence of Ha-RasV12-induced YAP activation. Surprisingly, the activation of YAP is not required for Ha-RasV12-induced multilayer cellular aggregates. Instead, Ha-RasV12 triggered the ERK-Rac pathway to promote cellular aggregate formation. Moreover, the overexpression of constitutively active Rac is sufficient to trigger cellular aggregation in MDCK cells at the confluent stage. This highlights that Rac activity is essential for cellular aggregates.
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U2 - 10.3390/biomedicines10050977
DO - 10.3390/biomedicines10050977
M3 - Article
AN - SCOPUS:85129600490
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 5
M1 - 977
ER -