Pleckstrin-2 as a Prognostic Factor and Mediator of Gastric Cancer Progression

Abstract

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c‐Myc‐mediated positive feedback loop

“…Mechanistically, PLEK2 exerted strong tumor-promoting effects on HNSCC cells by hindering the interaction between c-Myc and FBXW7, which subsequently enhanced c-Myc stability. Additionally, c-Myc Although previous studies have revealed that abnormal expression of PLEK2 is associated with poor clinical outcomes in some types of cancer [9,12], its expression pattern and clinical significance in HNSCC remain unknown. A recent bioinformatics analysis of public datasets demonstrated that PLEK2 might be a potential molecular target for HNSCC [20].…”

“…Although aberrant expression of PLEK2 has been shown to play a critical role in regulating many important biological processes such as inflammation, erythropoiesis and tumorigenesis [ 7 , 8 , 9 ], its underlying cellular and molecular mechanisms remain poorly understood. PLEK2 was reported to be highly expressed in several malignancies, including non‐small cell lung cancer [ 10 ], gallbladder cancer [ 11 ] and gastric cancer [ 12 ], while low PLEK2 mRNA levels were observed in multiple myeloma bone marrow progenitor cells [ 13 ] and prostate cancer [ 14 ]. These findings indicate that the biological functions of PLEK2 might be tumor type‐dependent and closely related to the tumor microenvironment in which cancer cells reside.…”

Emerging Roles of Pleckstrin-2 Beyond Cell Spreading

“…Increasing evidences suggest that PLEK2 plays a cancerpromoting role in tumorigenesis and metastasis (Table 3). PLEK2 expression has been demonstrated to be highly upregulated in several malignancies, and its knockdown leads to the inhibition of cancer cell proliferation, migration and invasion, including non-small cell lung cancer (Wu et al, 2020), gallbladder cancer (Shen et al, 2019), osteosarcoma (Liu et al, 2021), pancreatic cancer (Yang et al, 2021), gastric cancer (Wang et al, 2021a), and esophageal squamous cell carcinoma (Wang et al, 2021).…”

“…Increasing evidences suggest that PLEK2 plays a cancer-promoting role in tumorigenesis and metastasis ( Table 3 ). PLEK2 expression has been demonstrated to be highly upregulated in several malignancies, and its knockdown leads to the inhibition of cancer cell proliferation, migration and invasion, including non-small cell lung cancer ( Wu et al, 2020 ), gallbladder cancer ( Shen et al, 2019 ), osteosarcoma ( Liu et al, 2021 ), pancreatic cancer ( Yang et al, 2021 ), gastric cancer ( Wang et al, 2021a ), and esophageal squamous cell carcinoma ( Wang et al, 2021 ). Although two recent studies showed that PLEK2 mRNA expression is down-regulated in multiple myeloma bone marrow progenitor cells and prostate cancer, its expression is thought to be positively correlated with the poor prognosis ( Wang et al, 2020 ; Yang et al, 2020 ).…”

“…Recently, roles of PLEK2 in other cellular events beyond cell spreading are gradually being identified. Several lines of evidences suggest that PLEK2 is a potential therapeutic target for the treatment of cancers ( Zhao et al, 2018 ; Shen et al, 2019 ; Wu et al, 2020 ; Liu et al, 2021 ; Wang et al, 2021a ; Yang et al, 2021 ).…”