Role of the autotaxin–lysophosphatidate axis in the development of resistance to cancer therapy

Tang, Xiaoyun; Benesch, Matthew G.K.; Brindley, David N.

doi:10.1016/j.bbalip.2020.158716

Cited by 27 publications

(24 citation statements)

References 246 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intracellular LPA is generated by intracellular phospholipases A1 and A2, glycerol 3‐phosphate acyltransferase, or monoacylglycerol kinase 45 . A role for autoxin and phospholipases A1/A2 in cancer progression has been suggested 46,47 . Analysis of clinical data has indicated an increased level of LPA in cancer, suggesting that LPA may serve as a diagnosis or prognosis biomarker for cancer 48,49 .…”

Section: Dysregulation Of Lipid Metabolism In Cancermentioning

confidence: 99%

Lipid metabolism in cancer progression and therapeutic strategies

Zou

Shen

et al. 2020

MedComm

154

113

View full text Add to dashboard Cite

Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression. The rewiring of lipid metabolism in cancer has been linked to the activation of oncogenic signaling pathways and cross talk with the tumor microenvironment. The resulting activity favors the survival and proliferation of tumor cells in the harsh conditions within the tumor. Lipid metabolism also plays a vital role in tumor immunogenicity via effects on the function of the noncancer cells within the tumor microenvironment, especially immune‐associated cells. Targeting altered lipid metabolism pathways has shown potential as a promising anticancer therapy. Here, we review recent evidence implicating the contribution of lipid metabolic reprogramming in cancer to cancer progression, and discuss the molecular mechanisms underlying lipid metabolism rewiring in cancer, and potential therapeutic strategies directed toward lipid metabolism in cancer. This review sheds new light to fully understanding of the role of lipid metabolic reprogramming in the context of cancer and provides valuable clues on therapeutic strategies targeting lipid metabolism in cancer.

show abstract

Section: Dysregulation Of Lipid Metabolism In Cancermentioning

confidence: 99%

Lipid metabolism in cancer progression and therapeutic strategies

Zou

Shen

et al. 2020

MedComm

154

113

View full text Add to dashboard Cite

show abstract

“…ATX generates LPA through hydrolyzing LPC, which is enriched in plasma and bronchoalveolar lavage. ATX is a secreted glycoprotein and its level changes in various human disorders including lung diseases and cancer [1,24,25]. Another source of extracellular LPA is from activation of secretory PLA 2 [26].…”

Section: Biosynthesis Of Lpamentioning

confidence: 99%

Lysophospholipids in Lung Inflammatory Diseases

Zhao

2021

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

The lysophospholipids (LPLs) belong to a group of bioactive lipids that play pivotal roles in several physiological and pathological processes. LPLs are derivatives of phospholipids and consist of a single hydrophobic fatty acid chain, a hydrophilic head, and a phosphate group with or without a large molecule attached. Among the LPLs, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are the simplest, and have been shown to be involved in lung inflammatory symptoms and diseases such as acute lung injury, asthma, and chronic obstructive pulmonary diseases. G protein-coupled receptors (GPCRs) mediate LPA and S1P signaling. In this chapter, we will discuss on the role of LPA, S1P, their metabolizing enzymes, inhibitors or agonists of their receptors, and their GPCR-mediated signaling in lung inflammatory symptoms and diseases, focusing specially on acute respiratory distress syndrome, asthma, and chronic obstructive pulmonary disease.

show abstract

“…LPA also increases vascular endothelial growth factor (VEGF) production, which stimulates the angiogenesis needed for tumor growth [ 50 ]. LPA signaling is generally increased in cancers because of the high secretion of ATX and the low expressions of LPP1 and LPP3 [ 51 ]. ATX concentrations are correlated with invasiveness [ 8 , 10 , 52 ] and the ATX gene ( ENPP2 ) is among the 40–50 most up-regulated genes in metastatic tumors [ 53 , 54 , 55 ].…”

Section: Role Of Atx Activity In Wound Healing Chronic Inflammatimentioning

confidence: 99%

“…Low expression of mRNA for LPP1 is one of 12 changes in mRNA that predicts poor survival in breast cancer patients [ 103 ]. We showed that mRNA concentrations for LPP1 were lower in all types of breast tumors compared to normal breast tissue [ 27 , 51 ].…”

Section: Role Of Lipid Phosphate Phosphatases In Controlling Lpa Smentioning

confidence: 99%

Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer

Brindley

Tang

Meng

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Autotaxin (ATX) is a secreted enzyme that produces lysophosphatidate (LPA), which signals through six G-protein coupled receptors, promoting tumor growth, metastasis, and survival from chemotherapy and radiotherapy. Many cancer cells produce ATX, but breast cancer cells express little ATX. In breast tumors, ATX is produced by tumor-associated stroma. Breast tumors are also surrounded by adipose tissue, which is a major bodily source of ATX. In mice, a high-fat diet increases adipocyte ATX production. ATX production in obesity is also increased because of low-level inflammation in the expanded adipose tissue. This increased ATX secretion and consequent LPA signaling is associated with decreased adiponectin production, which results in adverse metabolic profiles and glucose homeostasis. Increased ATX production by inflamed adipose tissue may explain the obesity-breast cancer association. Breast tumors produce inflammatory mediators that stimulate ATX transcription in tumor-adjacent adipose tissue. This drives a feedforward inflammatory cycle since increased LPA signaling increases production of more inflammatory mediators and cyclooxygenase-2. Inhibiting ATX activity, which has implications in breast cancer adjuvant treatments, attenuates this cycle. Targeting ATX activity and LPA signaling may potentially increase chemotherapy and radiotherapy efficacy, and decrease radiation-induced fibrosis morbidity independently of breast cancer type because most ATX is not derived from breast cancer cells.

show abstract

Role of the autotaxin–lysophosphatidate axis in the development of resistance to cancer therapy

Cited by 27 publications

References 246 publications

Lipid metabolism in cancer progression and therapeutic strategies

Lipid metabolism in cancer progression and therapeutic strategies

Lysophospholipids in Lung Inflammatory Diseases

Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer

Contact Info

Product

Resources

About