X‐ray‐enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex

Abstract

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation‐enhanced cell migration and invasion. A sublethal dose of X‐ray radiation promoted human breast cancer MDA‐MB‐231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose‐dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X‐ray‐enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X‐ray‐enhanced migration and invasion. In addition, the results suggested that X‐ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon‐enhanced cell migration and invasion.

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway

“…Ionizing radiation promotes cell migration at sub-lethal doses ( 115 – 118 ). The linker of nucleoskeleton and cytoskeleton complex is responsible for both radiation-induced cell migration ( 119 ) and NE ruptures ( 120 ). Therefore, NE ruptures may become more likely following radiation exposure.…”

The SUN1 splicing variants SUN1_888 and SUN1_916 differentially regulate nucleolar structure

“…First, to verify the contributions of SUN1 to nucleolar morphology in hTERT‐RPE1 cells, all SUN1 splicing variants were depleted using a pool of siRNAs (siSUN1, Figure 1b) and stained with anti‐UBF mAb, which is a specific marker for the FC region in the nucleolus (Roussel et al, 1996). Knockdown efficiency was confirmed by immunofluorescence microscopy (Figure 1b) and Western blotting (Imaizumi et al, 2018; Nishioka et al, 2016). We typically observed an average of three discrete round nucleoli in each nucleus in the negative control siRNA (siNC)‐transfected cells, whereas cells depleted of all of the SUN1 splicing variants showed an average of four nucleoli with a modestly irregular shape per nucleus (Figure 1b,c).…”

Comprehensive circular RNA expression profile in radiation-treated HeLa cells and analysis of radioresistance-related circRNAs

“…Many studies have shown that radiation can kill tumor cells and promote cell migration and invasion via different mechanisms. It was shown that sublethal X-ray can enhance cell migration ( Imaizumi et al, 2018 ). Another study found that the higher was radioresistance, the higher was the expression of VEGFR , which might lead to fast angiogenesis ( Lee et al, 2017 ).…”