Phospholipase D as a key modulator of cancer progression

Yao, Yuanfa; Wang, Xinyi; Li, Hanbing; Fan, Jiannan; Qian, Xiaohan; Li, Hong; Xu, Yingke

doi:10.1111/brv.12592

Cited by 40 publications

(30 citation statements)

References 172 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the predominant ways that S1P can signal within the cell is through phospholipase-mediated pathways. Phospholipases C (PLC) and D (PLD) have emerged as major contributors to the aggressive phenotypes seen in GBM including invasion and chemoresistance, as well as promotion of metastasis in other cancer types [109][110][111][112]. The intersection between sphingolipid metabolism and phospholipase signaling provides a greater understanding of how these pathways synergize to promote cancer progression in both GBM and metastatic cancers.…”

Section: Phospholipase-mediated Signalingmentioning

confidence: 99%

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

et al. 2020

View full text Add to dashboard Cite

Glioblastoma (GBM) is a primary malignant brain tumor with a dismal prognosis, partially due to our inability to completely remove and kill all GBM cells. Rapid tumor recurrence contributes to a median survival of only 15 months with the current standard of care which includes maximal surgical resection, radiation, and temozolomide (TMZ), a blood–brain barrier (BBB) penetrant chemotherapy. Radiation and TMZ cause sphingomyelinases (SMase) to hydrolyze sphingomyelins to generate ceramides, which induce apoptosis. However, cells can evade apoptosis by converting ceramides to sphingosine-1-phosphate (S1P). S1P has been implicated in a wide range of cancers including GBM. Upregulation of S1P has been linked to the proliferation and invasion of GBM and other cancers that display a propensity for brain metastasis. To mediate their biological effects, SMases and S1P modulate signaling via phospholipase C (PLC) and phospholipase D (PLD). In addition, both SMase and S1P may alter the integrity of the BBB leading to infiltration of tumor-promoting immune populations. SMase activity has been associated with tumor evasion of the immune system, while S1P creates a gradient for trafficking of innate and adaptive immune cells. This review will explore the role of sphingolipid metabolism and pharmacological interventions in GBM and metastatic brain tumors with a focus on SMase and S1P.

show abstract

Section: Phospholipase-mediated Signalingmentioning

confidence: 99%

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These functions contribute to numerous disease conditions, including neurodegeneration, inflammation, and cancer [ 5 ]. PLD upregulation occurs in various tumors, including renal, brain, breast, gastric, thyroid, colorectal, and expression correlated with various predictive measures [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer

Liu¹,

Li²,

Ma³

et al. 2021

Bioengineered

View full text Add to dashboard Cite

Prostate cancer (PCa), a frequently detected malignant tumor, is the fifth leading global cancer mortality cause in men. Although research has improved the PCa survival rate, significantly reduced survival occurs among patients at the metastatic stage. MiRNAs, which are short noncoding proteins, are crucial for several biological roles, essential for PCa proliferation, differentiation, multiplication, and migration. The investigation aimed to explore miR-145-5p and PLD5 association and clarify their function in regulating proliferation in PCa cell lines.The study used PC-3, LNCaP, DU-145 PCa, and RWPE-1 non-cancerous cell line, PCa, and BPH tissue specimens, and nude mice to validate results. MiR-145-5p and PLD5 manifestation were assessed through RT-qPCR. PLD5 and miR-145 binding was determined through dual-luciferase reporter gene assays. Validation of cell proliferation, migration, and invasion was assessed through MTT, scratch wound, and transwell assays, respectively. The results indicated a downregulation of miR-145-5p level in PCa cell lines and tissues in comparison to the non-cancerous controls. PLD5 overexpression exerted a cancerous effect while mimicking of miR-145-5p reversed the PLD5-oncogenic effects and significantly inhibited PCa cells proliferation, migration, invasion, and metastasis. In conclusion, the study revealed that miR-145-5p upregulated apoptosis and repressed migration, invasion, and metastasis of PCa via direct PLD5 modulation.

show abstract

“…Concurrently, a positive association was identified between LAMP2A and PLD2. 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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

Chaperone-mediated autophagy (CMA) is a selective type of autophagy whereby a specific subset of intracellular proteins is targeted to the lysosome for degradation. The present study investigated the mechanisms underlying the response and resistance to 5-fluorouracil (5-FU) in colorectal cancer (CRC) cell lines. In engineered 5-FU-resistant CRC cell lines, a significant elevation of lysosome-associated membrane protein 2A (LAMP2A), which is the key molecule in the CMA pathway, was identified. High expression of LAMP2A was found to be responsible for 5-FU resistance and to enhance PLD2 expression through the activation of NF-κB pathway. Accordingly, loss or gain of function of LAMP2A in 5-FU-resistant CRC cells rendered them sensitive or resistant to 5-FU, respectively. Taken together, the results of the present study suggested that chemoresistance in patients with CRC may be mediated by enhancing CMA. Thus, CMA is a promising predictor of chemosensitivity to 5-FU treatment and anti-CMA therapy may be a novel therapeutic option for patients with CRC.

show abstract

Phospholipase D as a key modulator of cancer progression

Cited by 40 publications

References 172 publications

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

MicroRNA miR-145-5p inhibits Phospholipase D 5 (PLD5) to downregulate cell proliferation and metastasis to mitigate prostate cancer

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

Contact Info

Product

Resources

About