Phosphorylation of AKT by lysyl oxidase-like 2 activates the PI3K/AKT signaling pathway to promote proliferation, invasion and metastasis in esophageal squamous carcinoma.

Content Provider	Europe PMC
Author	Fan, Zhiqin Liu, Yingmin Liu, Xinya Nian, Wei Huang, Xiaotong Yang, Qianqian Hou, Songyu Chen, Fei
Abstract	ObjectiveEsophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy of the gastrointestinal tract for which therapeutic options are scarce. This study screens for LOXL2, a key gene in ESCC, and explains the molecular mechanism by which it promotes the progression of ESCC.MethodsImmunohistochemical staining was performed to detect the expression level of LOXL2 in ESCC tissues and paraneoplastic tissues. CCK-8 and Transwell assays were performed to assess the effects of LOXL2 knockdown and overexpression on the proliferation, apoptosis, migration and invasion ability of ESCC cells. High-throughput sequencing analysis screens for molecular mechanisms of action by which LOXL2 promotes ESCC progression. Western blotting and qRT-PCR were used to determine the expression levels of relevant markers.ResultsLOXL2 is positively expressed in ESCC and highly correlated with poor prognosis. Silencing LOXL2 significantly inhibited the proliferation, migration and invasive ability of ESCC cells, whereas overexpression showed the opposite phenotype. High-throughput sequencing suggested that LOXL2-associated differentially expressed genes were highly enriched in the PI3K/AKT signaling pathway. In vitro cellular assays confirmed that silencing LOXL2 significantly reduced PI3K, p-AKTThr308 and p-AKTSer473 gene and protein expression levels, while overexpression increased all three gene and protein levels, while AKT gene and protein expression levels were not significantly different.ConclusionThis study found that LOXL2 may regulate the PI3K/AKT signaling pathway and exert protumor effects on ESCC cells through phosphorylation of AKT. LOXL2 may be a key clinical warning biomarker or therapeutic target for ESCC.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC10293450&blobtype=pdf
ISSN	1699048X
Journal	Clinical & Translational Oncology [Clin Transl Oncol]
Volume Number	25
DOI	10.1007/s12094-023-03133-5
PubMed Central reference number	PMC10293450
Issue Number	8
PubMed reference number	36995521
e-ISSN	16993055
Language	English
Publisher	Springer International Publishing
Publisher Date	2023-03-30
Publisher Place	Gewerbestrasse 11, Cham, Ch 6330, Switzerland
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2023
Subject Keyword	ESCC LOXL2 Phosphorylation of AKT PI3K/AKT signaling pathway Proliferation Invasion Metastasis
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology