S100A16 stabilizes the ITGA3‑mediated ECM‑receptor interaction pathway to drive the malignant properties of lung adenocarcinoma cells via binding MOV10

Abstract

Lung adenocarcinoma (LUAD) is highly associated with lung cancer-associated mortality. Notably, S100 calcium-binding protein A16 (S100A16) has been increasingly considered to have prognostic value in LUAD; however, the underlying mechanism remains unknown. In the present study, S100A16 expression levels in LUAD tissues and cells were respectively analyzed by the UALCAN database and western blotting. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to examine cell proliferation, whereas wound healing, Transwell and tube formation assays were used to assess cell migration, invasion and angiogenesis, respectively. Western blotting was also used to examine the expression levels of proteins associated with metastasis, angiogenesis, focal adhesion and the extracellular matrix (ECM)-receptor interaction pathways. The relationship between S100A16 and Mov10 RNA helicase (MOV10) was predicted by bioinformatics tools, and was verified using a co-immunoprecipitation assay. Furthermore, the interaction between MOV10 and integrin α3 (ITGA3) was verified by RNA immunoprecipitation assay, and the actinomycin D assay was used to detect ITGA3 mRNA stability. The results demonstrated that S100A16 expression was increased in LUAD tissues and cell lines, and was associated with unfavorable outcomes. Knocking down S100A16 expression hindered the proliferation, migration, invasion and angiogenesis of LUAD cells. Furthermore, S100A16 was shown to bind to MOV10 and positively modulate MOV10 expression in LUAD cells, while MOV10 overexpression partially reversed the suppressive role of S100A16 knockdown on the aggressive phenotypes of LUAD cells. Furthermore, it was demonstrated that S100A16 regulated the stability of ITGA3 mRNA via MOV10 to mediate ECM-receptor interactions. In conclusion, S100A16 may bind to MOV10 to stabilize ITGA3 mRNA and regulate ECM-receptor interactions, hence contributing to the malignant progression of LUAD.

Single-Cell Dissection Identifies METTL7B as Associated with Cell Adhesion-Mediated Tumor Invasion in Lung Adenocarcinoma and Glioblastoma

“…In LUAD, early disease appears to co-opt a transitional injury/plasticity state dependent on a KRAS-ITGA3-SRC axis [ 32 ], suggesting ITGA3 contributes to the initiation-phase circuitry. At the post-transcriptional level, S100A16 stabilizes ITGA3 mRNA via MOV10 to maintain ECM-receptor signaling and malignant phenotypes in LUAD [ 33 ]. In glioblastoma, nanoparticle-delivered si-lncRNA NONHSAT159592.1 suppresses proliferation, Epithelial–Mesenchymal Transition (EMT), and invasion through ITGA3-related pathway, and ITGA3 overexpression reverses these inhibitory effects [ 34 ], directly supporting an ITGA3-anchored pro-invasive signaling route.…”

Single-Cell Dissection Identifies METTL7B as Associated with Cell Adhesion-Mediated Tumor Invasion in Lung Adenocarcinoma and Glioblastoma

“…In LUAD, early disease appears to co-opt a transitional injury/plasticity state dependent on a KRAS-ITGA3-SRC axis [ 32 ], suggesting ITGA3 contributes to the initiation-phase circuitry. At the post-transcriptional level, S100A16 stabilizes ITGA3 mRNA via MOV10 to maintain ECM-receptor signaling and malignant phenotypes in LUAD [ 33 ]. In glioblastoma, nanoparticle-delivered si-lncRNA NONHSAT159592.1 suppresses proliferation, Epithelial–Mesenchymal Transition (EMT), and invasion through ITGA3-related pathway, and ITGA3 overexpression reverses these inhibitory effects [ 34 ], directly supporting an ITGA3-anchored pro-invasive signaling route.…”

Exosomal integrin alpha 3 promotes epithelial ovarian cancer cell migration via the S100A7/p-ERK signaling pathway

“…Recent research highlights a significant link between ITGA3 and the S100 family of calcium-binding proteins in cancer biology [27] , suggesting that these molecules may work together as potential biomarkers and therapeutic targets in various malignancies. Although the interactions between ITGA3, S100A7, and ERK in EOC are still underexplored, the presence of ITGA3 and S100A7 in exosomes indicates that they may synergistically promote tumor cell migration and invasion.…”

Single-Cell Dissection Identifies METTL7B as Associated with Cell Adhesion-Mediated Tumor Invasion in Lung Adenocarcinoma and Glioblastoma

“…In LUAD, early disease appears to co-opt a transitional injury/plasticity state dependent on a KRAS-ITGA3-SRC axis [ 32 ], suggesting ITGA3 contributes to the initiation-phase circuitry. At the post-transcriptional level, S100A16 stabilizes ITGA3 mRNA via MOV10 to maintain ECM-receptor signaling and malignant phenotypes in LUAD [ 33 ]. In glioblastoma, nanoparticle-delivered si-lncRNA NONHSAT159592.1 suppresses proliferation, Epithelial–Mesenchymal Transition (EMT), and invasion through ITGA3-related pathway, and ITGA3 overexpression reverses these inhibitory effects [ 34 ], directly supporting an ITGA3-anchored pro-invasive signaling route.…”

Exosomal integrin alpha 3 promotes epithelial ovarian cancer cell migration via the S100A7/p-ERK signaling pathway

“…Recent research highlights a significant link between ITGA3 and the S100 family of calcium-binding proteins in cancer biology [27] , suggesting that these molecules may work together as potential biomarkers and therapeutic targets in various malignancies. Although the interactions between ITGA3, S100A7, and ERK in EOC are still underexplored, the presence of ITGA3 and S100A7 in exosomes indicates that they may synergistically promote tumor cell migration and invasion.…”

Single-Cell Dissection Identifies METTL7B as Associated with Cell Adhesion-Mediated Tumor Invasion in Lung Adenocarcinoma and Glioblastoma

“…In LUAD, early disease appears to co-opt a transitional injury/plasticity state dependent on a KRAS-ITGA3-SRC axis [ 32 ], suggesting ITGA3 contributes to the initiation-phase circuitry. At the post-transcriptional level, S100A16 stabilizes ITGA3 mRNA via MOV10 to maintain ECM-receptor signaling and malignant phenotypes in LUAD [ 33 ]. In glioblastoma, nanoparticle-delivered si-lncRNA NONHSAT159592.1 suppresses proliferation, Epithelial–Mesenchymal Transition (EMT), and invasion through ITGA3-related pathway, and ITGA3 overexpression reverses these inhibitory effects [ 34 ], directly supporting an ITGA3-anchored pro-invasive signaling route.…”

Exosomal integrin alpha 3 promotes epithelial ovarian cancer cell migration via the S100A7/p-ERK signaling pathway

“…Recent research highlights a significant link between ITGA3 and the S100 family of calcium-binding proteins in cancer biology [27] , suggesting that these molecules may work together as potential biomarkers and therapeutic targets in various malignancies. Although the interactions between ITGA3, S100A7, and ERK in EOC are still underexplored, the presence of ITGA3 and S100A7 in exosomes indicates that they may synergistically promote tumor cell migration and invasion.…”