ANXA1–GSK3β interaction and its involvement in NSCLC metastasis

Abstract

Although initially discovered and extensively studied for its role in inflammation, Annexin A1 (ANXA1) has been reported to be closely related to cancer in recent years, and its role in cancer is specific to tumor types and tissues. In the present study, we identified ANXA1 as an interaction partner of glycogen synthase kinase 3 beta (GSK3β), a multi-functional serine/threonine kinase tightly associated with cell fate determination and cancer, and assessed the functional significance of GSK3β–ANXA1 interaction in the metastasis of non-small cell lung cancer (NSCLC). We confirmed the interaction between GSK3β and ANXA1 in vitro and in H1299 and A549 cells by Glutathione-S-transferase (GST) pull-down assay and co-immunoprecipitation. We found that ANXA1 negatively regulated the phosphorylation of GSK3β and inhibited the epithelial–mesenchymal transformation (EMT) process and migration and invasion of NSCLC cells. By functional rescue assay, we confirmed that ANXA1 inhibited EMT through the regulation of GSK3β activity and thereby inhibited the migration and invasion of NSCLC cells. Our study sheds light on the function of ANXA1 and GSK3β and provides new elements for the understanding of NSCLC pathogenesis.

DDX17 promotes the growth and metastasis of lung adenocarcinoma

“…Western-blot assays were used to analyze protein expression [ 44 ]. The following antibodies were used: DDX17 (Proteintech, Cat.…”

“…qRT - PCR was performed with the SYBR Green Supermix (Bio-Rad, Hercules, USA) according to standard protocols [ 44 ]. Housekeeping gene GAPDH was used as an internal control.…”

ZSWIM1 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma Cells through the STK38/MEKK2/ERK1/2 Axis

“…The transwell assay was performed as previously described to test migration and invasion . For the invasion assay, the chambers were coated with 100 μL of dissolved Matrigel (Corning, USA, Matrigel: DMEM = 1:10–1:20) in a 37 °C incubator for 30 min.…”

“…The transwell assay was performed as previously described to test migration and invasion. 9 For the invasion assay, the chambers were coated with 100 μL of dissolved Matrigel (Corning, USA, Matrigel: DMEM = 1:10−1:20) in a 37 °C incubator for 30 min. Cells after the corresponding treatments were implanted with 8 × 10 4 cells/well in 200 μL of serum-free DMEM in the upper chamber, and the bottom chamber was filled with 800 μL of DMEM containing 10% FBS.…”

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review

“…High ANXA1 expression is positively correlated with tumor metastasis, which is mainly manifested in PC ( 18 , 19 ), melanoma ( 32 ), NPC ( 11 , 12 ), PTC ( 25 ), and positive BC ( 51 - 53 ). However, the downregulation of ANXA1 has been confirmed to be associated with the distant metastasis of NSCLC ( 54 ) as well as the metastatic mouse and human BC cell lines ( 37 , 55 , 56 ). At present, the expression and functional roles of ANXA1 in BC remain controversial ( 53 , 57 ).…”