Alpha Protein Kinase 2 Promotes Esophageal Cancer via Integrin Alpha 11

Abstract

Background. As a common disease around the world, esophageal cancer (EC) primarily includes two subclasses: esophageal adenocarcinoma and esophageal squamous cell carcinoma. Mortality has been rising over the years; hence, exploring the mechanism of EC development has become critical. Among the alpha protein kinases, alpha protein kinase 2 (ALPK2) presumably has a connection with EC, but it has never been revealed before. Methods. In this study, IHC analysis was used for ALPK2 expression quantification in ES tissues. TE-1 and Eca-109, which are both human EC cell lines, were used for in vitro analysis of cell proliferation, migration, apoptosis, and colony formation. Results. ALPK2 was found to have an abundant expression within EC tissues ( P < 0.001 ), as well as in the two selected human EC cell lines ( P < 0.05 ). The data showed that ALPK2 depletion suppressed EC cell proliferation, migration, and colony formation, meanwhile stimulating apoptosis ( P < 0.001 ). The in vivo experiments also displayed inhibitory effects caused by ALPK2 depletion on EC tumorigenesis ( P < 0.001 ). It was further validated that ALPK2 depletion made the phosphorylation of Akt and mTOR, as well as CDK6 and PIK3CA levels downregulated ( P < 0.001 ). Mechanistically, we identified integrin alpha 11 (ITGA11) as a downstream gene of ALPK2 regulating EC. More importantly, we found that ITGA11 elevation promoted cell proliferation and migration and rescued the suppression effects caused by ALPK2 depletion ( P < 0.001 ). Conclusions. ALPK2 promotes esophageal cancer via integrin its downstream gene alpha 11; ALPK2 can potentially act as a target for the treatment of EC.

The Influence of Alpha Kinase 2 Expression on Prognosis in Serous Ovarian Cancer Liver Metastasis

“…Elevated ALPK2 levels signifcantly diminished overall survival in OCLM patients, aligning with prior studies associating increased ALPK2 expression with aggressive tumor behavior in other cancer types [18]. Tis suggests that ALPK2 may not only serve as a prognostic marker but could also potentially act as a mechanistic driver of tumor progression [10][11][12]. Te signifcance of age as a factor afecting overall survival emphasizes the importance of early detection and targeted interventions.…”

“…Te signalling mechanisms through which ALPK2 operates in this context are yet to be fully elucidated, but its involvement suggests a potential regulatory role in pathways governing cell proliferation and metastasis [9]. Similarly, ALPK2 has been implicated in promoting aggressiveness through multiple signalling pathways in bladder cancer, esophageal cancer, and nonsmall lung cancer [10][11][12]. Te precise molecular mechanisms by which ALPK2 contributes to tumor progression involve intricate crosstalk with signalling cascades associated with increased cell motility, invasion, and resistance to apoptosis.…”

Mechanisms of esophageal cancer metastasis and treatment progress

“…Ainiwaer et al. found that ALPK2, as a downstream target gene, promotes ESCC tumor cell migration in vascular endothelial cells by regulating ITGα11 ( 62 ) ( Figure 1 ).…”

ITGA11, a Prognostic Factor Associated with Immunity in Gastric Adenocarcinoma

“…ITGA11 influences prognosis by promoting cancer-associated fibroblast (CAF) migration. [6][7][8][9][10][11][12][13][14] Furthermore, ITGA11 is critical in myofibroblast differentiation, matrix reorganization, and collagen deposition. 15,16 ITGA11 is overexpressed in CAFs, contributing to tumor matrix construction and affecting the overall survival of patients with head and neck squamous cell carcinoma.…”