p21‐activated kinase 4 promotes the progression of esophageal squamous cell carcinoma by targeting LASP1

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the digestive tract in humans. Several studies have indicated that PAK4 is associated with the risk of ESCC and may be a potential druggable kinase for ESCC treatment. However, the underlying mechanism remains largely unknown. The aim of our study is to identify the functional role of PAK4 in ESCC. To determine the expression of PAK4 in ESCC, Western blot analysis and immunohistochemistry were performed, and the results showed that PAK4 is significantly upregulated in ESCC tissues and cell lines compared with normal controls and normal esophageal epithelial cell line. To further investigate the role of PAK4 in ESCC, cell viability assays, anchorage‐independent cell growth assays, wound healing assays, cellular invasion assays, in vivo xenograft mouse models, and metastasis assays were conducted, and the results showed that PAK4 can significantly facilitate ESCC proliferation and metastasis in vitro and in vivo. To determine the potential target of PAK4 in ESCC progression, a pull‐down assay was performed, and the results showed that LASP1 may be a potential target of PAK4. An immunoprecipitation assay and confocal microscopy analysis confirmed that PAK4 can bind to and colocalize with LASP1 in vitro and in cells. Notably, rescue experiments further illustrated the mechanistic network of PAK4/LASP1. Our research reveals the oncogenic roles of PAK4 in ESCC and preliminarily elucidates the mechanistic network of PAK4/LASP1 in ESCC.

Comprehensive analysis of immune cell enrichment in the tumor microenvironment of head and neck squamous cell carcinoma

“…HSNCC is highly infiltrated by immune cells, including tumor-infiltrating lymphocytes (TILs) and myeloid lineage cells 11 , 12 . In the TME of HNSCC, tumor cells reportedly orchestrate a highly immunosuppressive state by secreting immunosuppressive mediators, expressing immune checkpoint ligands, and downregulating human leukocyte antigen expression 13 , 14 . These tumor cell behaviors result in the dysfunction and exhaustion of cytotoxic T lymphocytes (CTLs), as well as increased infiltration and activation of immunosuppressive cell types, such as regulatory T cells (Tregs), tumor-associated macrophages, and myeloid-derived suppressor cells (MDSCs) 15 .…”

Upregulated glycolysis correlates with tumor progression and immune evasion in head and neck squamous cell carcinoma

“…However, the survival benefit is limited to only 20–30% patients, and new biomarkers that predict the efficacy of anti-PD-1 therapy have been investigated. Accumulating evidence has indicated that in HNSCC, tumor cells orchestrate a highly immunosuppressive tumor microenvironment (TME) via the production of immunosuppressive mediators, recruitment of various stromal cells, expression of immune checkpoint ligands, and downregulation of human leukocyte antigen expression 7 , 8 , which is referred to as immune evasion 9 . As immune checkpoint inhibitors, including anti-PD-1 antibodies, target the interaction between tumor cells and T cells, a comprehensive understanding of complex immune networks in the TME is needed to establish a new biomarker for immunotherapies.…”

MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs

“…In cellular experiments, miR-206 inhibited the proliferation, migration and invasion of the HUCCT1 and RBE cell lines. LASP1 (LIM and SH3 domain protein 1) was recently identified as a regulator of tumor progression and drug resistance in several cancers, including CCA [25][26][27][28]. In this study, LASP1 was proven to be a target of miR-206 and promoted Nanog and TGF-beta1 expression via the STAT3 pathway.…”