High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of Colon Cancer Cells through Activating NF- κ Bp65 Signaling Pathway

Abstract

Hypoxia is a typical feature of colon cancer occurrence and progression. We have reported that high expression and activity of PhospholipaseD2 (PLD2) induced by hypoxia in colon cancer cells. In order to further investigate the role of PLD2 in colon cancer under hypoxic conditions. MTT assay was used to detect the proliferation of human colon cancer cells (SW480 and SW620) under hypoxic conditions by decrease the PLD2 gene expression or inhibit the activity of PLD2. Expression level of p-P65/T-P65 and Cyclin D1 were detected in those cells treated as above through using western blot and RT-PCR analysis. Effect of NF-Bp65 inhibitor (BAY-117082) on the proliferation and expression level of Cyclin D1 and PLD2 of colon cancer cells under hypoxic conditions were further analysised. As a result, decreased the expression of PLD2 or inhibited the activity of PLD2 leaded to the proliferation of hypoxia colon cancer cells reduced, and along with the expression level of p-P65/T-P65 and Cyclin D1 reduced. However, inhibition the expression level of p-P65/T-P65 lead to the proliferation and expression of Cyclin D1 in those hypoxia colon cancer cells also reduced. In vivo growth decreased in response to PLD2 and NF-Bp65 inhibition. Our study indicates that high expression of PLD2 induced by hypoxia promotes the proliferation of colon cancer cells, and it may elevate the expression level of Cyclin D1 through activating NF-Bp65 signaling pathway. Inhibition of the PLD2 expression may provide a new clue for treatment for colon cancer.

Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy

“…In our study, we found that lipid metabolism was significantly down-regulated in HR-MUT. Beyond our own results, other studies have confirmed that lipid metabolism rearrangement is involved in the regulation of the CRC cell chemotherapy resistance mechanism ( Fiucci et al, 2000 ; Cotte et al, 2018 ), plays a role in the occurrence and development of CRC ( Hwang et al, 2014 ; Liu et al, 2016 ; Mihajlovic et al, 2019 ; Liu et al, 2020 ), and has an impact on the prognosis ( de Figueiredo Junior et al, 2018 ). Research has also found that lipid droplets (LD) levels in CRC cells are significantly higher than in those of normal cells, indicating that it may play a key role in the development of CRC ( Accioly et al, 2008 ).…”

“…Research has also found that lipid droplets (LD) levels in CRC cells are significantly higher than in those of normal cells, indicating that it may play a key role in the development of CRC ( Accioly et al, 2008 ). Many studies have confirmed that lipid metabolism-related enzymes participate in the occurrence and development of CRC ( Liu et al, 2020 ), regulate cell proliferation and invasion ( Sánchez-Martínez et al, 2015 ; Nath and Chan, 2016 ), and participate in drug resistance ( Fiucci et al, 2000 ; Cotte et al, 2018 ). Because of this, fatty acids, phospholipids, and cholesterol are synthesized actively, and their concentrations are significantly increased in tumor tissues ( Janardhan et al, 2006 ; Lupu and Menendez, 2006 ).…”

Inhibition of chaperone‑mediated autophagy reduces tumor growth and metastasis and promotes drug sensitivity in colorectal cancer

“…PLD2 is one of the two isoforms of PLD in mammals, which catalyzes the hydrolysis of the diester bond of phospholipids to generate PA and the free lipid headgroup (39). PLD2 expression is elevated in a number of human tumors and is highly variable (16,(19)(20)(21)(22). In CRC, the expression level of PLD2 was significantly associated with tumor size and survival of patients, which suggests that PLD2 may be a target for therapy in CRC (40).…”

“…A total of two mammalian isoforms of PLD have been described; PLD1 and PLD2, which are almost ubiquitous and share ~50% homology (17,18). PLD2 overexpression increases proliferation, adhesion, invasion and metastasis in a wide variety of cancers including gastric, colorectal, renal, stomach, lung and breast cancers (16,(19)(20)(21)(22). In addition, it has been reported that PLD2 is associated with multidrug resistance in human cancer cells (23).…”

ACTN4 Promotes the Proliferation, Migration, Metastasis of Osteosarcoma and Enhances its Invasive Ability through the NF-κB Pathway

“…After phosphorylation, p65 binds to p50 to form a heterodimer and is transferred to the nucleus to initiate downstream gene transcription. Studies have shown that aberrantly activated p65 (RelA) contributes to tumor development and progression [19,20]. In addition, the existence of co-immunoprecipitation between p65 and ACTN4 in non-small lung carcinoma cells has been reported [21].…”