Nuclear Softness Promotes the Metastatic Potential of Large-Nucleated Colorectal Cancer Cells via the ErbB4-Akt1-Lamin A/C Signaling Pathway
Yangkun Li, Qilin Li, Lei Mu, Yibing Hu, Chang Yan, Hui Zhao, Yulong Mi, Xiaolan Li, Deding Tao, Jichao Qin
Abstract
. Mechanistically, ErbB4 was highly expressed in LNCs, which phosphorylated lamin A/C at serine 22 via the ErbB4-Akt1 signaling pathway. Furthermore, the level of phosphorylated lamin A/C was a negative determinant of nuclear stiffness. Taken together, CRC LNCs possessed greater constricted migratory and metastatic potential than SNCs due to ErbB4-Akt1-mediated lamin A/C phosphorylation and nuclear softening. These results may provide a potential treatment strategy for tumor metastasis by targeting nuclear stiffness in patients with cancer, particularly CRC.
Topics & Concepts
LaminColorectal cancerCancer researchERBB4AKT1Signal transductionBiologyChemistryCell biologyCancerGeneticsPI3K/AKT/mTOR pathwayNucleusReceptor tyrosine kinaseNuclear Structure and FunctionCell death mechanisms and regulationRNA Research and Splicing