Galectin‑1 binds GRP78 to promote the proliferation and metastasis of gastric cancer

Abstract

The present study aimed to investigate the potential molecular mechanisms by which galectin-1 (Gal-1) and glucose-regulated protein 78 (GRP78) influence the development of malignant gastric cancer (GC). Immunohistochemistry and western blotting were used to map the expression and location of the Gal-1 gene in the 80 paraffin-embedded GC samples, 16 fresh samples and surrounding tissues. Gal-1 was overexpressed and knocked down using lentiviral vectors in the human GC cell lines HGC-27 and AGS. Through the use of the Cell Counting Kit-8 assay, clone formation assay, wound healing assay, invasion assay and tumor xenograft, the possible biological roles of Gal-1 were further evaluated. The downstream interacting proteins were predicted by the BioGRID database, and GRP78 was chosen for further investigation. Immunofluorescence labeling and Co-IP were used to confirm the connection. The statistical tests utilized were the two-tailed paired Student's t-test, χ 2 test, Kaplan-Meier and Cox regression analysis, and Spearman's rank correlation coefficients. In GC, Gal-1 is extensively expressed and has the potential to interact with GRP78. Poor prognosis is linked to high levels of GRP78 and Gal-1 expression in patients with GC. According to the functional study, Gal-1 knockdown prevented cells from thriving and pushed Gal-1 expression, which aided in the proliferation, migration and invasion of GC. Gal-1 overexpression additionally aided the development of subcutaneous xenograft tumors. The mechanistic investigation proved that GRP78 and Gal-1 interacted, accelerating the course of GC. Gal-1 silencing had an inhibitory effect on the proliferation of HGC-27 cells that was removed by ectopic GRP78 expression, whereas the stimulating effects of Gal-1 overexpression in AGS cells were inhibited by GRP78 knockdown. In conclusion, Gal-1 interacts with GRP78 to facilitate the advancement of GC. The Gal-1/GRP78 axis is supported by the functional data of the present study as a possible GC treatment target.

Construction of EMT related prognostic signature for kidney renal clear cell carcinoma, through integrating bulk and single-cell gene expression profiles

“…Considering its most significant aberrant expression in vitro , we further focused on its functions and finally found that si-LGALS1 could inhibit the cell migration and invasion ability of KIRC, which might be involved in suppressing EMT process. Numerous studies have provided the consistent findings that it functioned as a tumor promoting factor in multiple cancers, such as in gastric cancer ( Zhang et al, 2022 ) and ovarian cancer ( Li et al, 2023b ). Collectively, all above evidences have directly or indirectly supported our findings, providing potential clues regarding the prognostic value of our EMT related signature of KIRC.…”

Hepatitis E Virus Seroprevalence Indicated a Significantly Increased Risk Selectively in Patients with Gastric Cancer among 17 Common Malignancies

“…In addition, previous investigations indicated that certain host factors such as HSPG, GRP78, and ATP5B were involved in the cell entry of HEV [ 31 ]. Moreover, GRP78 and ATP5B were expressed in normal gastric tissue and were good prognostic factors of gastric cancer according to the HPA (Human Protein Atlas) database and previous reports [ 32 , 33 ]. Thus, we have rationale to speculate that HEV infects gastric tissue by binding to receptors such as GRP78 and ATP5B and contributes to gastric cancer development.…”

New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19

“…DnaJ Heat Shock Protein Family (Hsp40) Member B11 (DNAJB11), a co-chaperone of HSPA5/BiP/GRP78 ( 33 ), was reported to promote the development of pancreatic cancer cells in vitro and in vivo by upregulating the HSPA5 expression and activating EGFR/MAPK pathway ( 34 ). Galectin−1, a small protein family member with an affinity for β-galactosides ( 35 ), was reported to bind HSPA5 to promote the proliferation and metastasis of gastric cancers in vitro and in vivo ( 36 ). Leucine zipper EF-hand-containing transmembrane protein-1 (LETM1) was disclosed to have its genomic deletions in Wolf–Hirschhorn syndrome (WHS) and revealed to regulate ion homeostasis, cell viability, mitochondrial morphology, as well as overexpression in different human cancers.…”