Alterations in complex lipids in tumor tissue of patients with colorectal cancer

Pakiet, Alicja; Sikora, Kinga; Kobiela, Jarek; Rostkowska, Olga; Mika, Adriana; Śledziński, Tomasz

doi:10.1186/s12944-021-01512-x

Cited by 17 publications

(23 citation statements)

References 69 publications

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“…The alkyl-lysophospholipid analogue edelfosine, resveratrol, miltefosine, and inhibitors of SM metabolism enzymes were used to alter tumor cell membrane fluidity and permeability and showed remarkable efficacy in preventing tumor progression [ 54 , 85 , 103 , 104 ]. Devising novel anticancer strategies based on the modulation of lipid metabolism and the composition of the cell membrane was recently advised for the treatment of cancer and overcoming drug resistance, pioneering a novel field named membrane-lipid therapy [ 104 – 106 ]. Combination of chemotherapeutic drugs and Cer is presently increasingly used for tumor treatment [ 47 , 51 , 107 – 109 ].…”

Section: Manipulating Sphingomyelin Metabolism For Cancer Controlmentioning

confidence: 99%

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

2021

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Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

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Section: Manipulating Sphingomyelin Metabolism For Cancer Controlmentioning

confidence: 99%

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

2021

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“…This study further reported TG signatures as a potential discriminant in differentiating tumour from non-cancerous tissue. Conversely to the accumulation of LDs, other recent studies have reported decreased TG levels in patient-derived CRC tissues compared to normal mucosa [ 39 , 55 ]. Mika et al reported reduced levels of TG in a study of 25 CRC tissue and patient-matched controls using 1 H-nuclear magnetic resonance ( 1 H-NMR) methods [ 55 ], while Pakiet et al observed decreases in 21 TG, 8 DG, and one MG lipid species and decreased overall TG content in an LC-MS study of 10 patient-derived CRC tissues compared to normal mucosa [ 39 ].…”

Section: The Role Of Lipids In Crcmentioning

confidence: 99%

Reprogrammed Lipid Metabolism and the Lipid-Associated Hallmarks of Colorectal Cancer

Salita

Rustam

Mouradov

et al. 2022

Cancers

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Lipids have diverse structures, with multifarious regulatory functions in membrane homeostasis and bioenergetic metabolism, in mediating functional protein–lipid and protein–protein interactions, as in cell signalling and proliferation. An increasing body of evidence supports the notion that aberrant lipid metabolism involving remodelling of cellular membrane structure and changes in energy homeostasis and signalling within cancer-associated pathways play a pivotal role in the onset, progression, and maintenance of colorectal cancer (CRC) and their tumorigenic properties. Recent advances in analytical lipidome analysis technologies have enabled the comprehensive identification and structural characterization of lipids and, consequently, our understanding of the role they play in tumour progression. However, despite progress in our understanding of cancer cell metabolism and lipidomics, the key lipid-associated changes in CRC have yet not been explicitly associated with the well-established ‘hallmarks of cancer’ defined by Hanahan and Weinberg. In this review, we summarize recent findings that highlight the role of reprogrammed lipid metabolism in CRC and use this growing body of evidence to propose eight lipid metabolism-associated hallmarks of colorectal cancer, and to emphasize their importance and linkages to the established cancer hallmarks.

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“…Relative reduction of PUFA and increased SFA over UFA incorporation are thought to protect from lipid peroxidation-mediated cell death and metabolic stress, by neutralizing reactive oxygen species (ROS) and thus increasing cell survival, tumor progression and metastasis [ 19 , 38 , 39 ]. De novo fatty acid synthesis in CRC was shown to increase lipid raft formation within cellular membranes and thereby modulate accessibility for signal transduction proteins and additionally, tumor tissues showed distinct enriched profiles of highly complex lipid species [ 38 , 40 , 41 , 42 ].…”

Section: Lipid Biology In Crcmentioning

confidence: 99%

“…Somatic cells compared to tumor cells normally take up extracellular, circulating FAs from dietary fats whereas lipid biosynthesis is usually restricted to hepatocytes, adipose tissue and mammary glands [ 43 , 44 ]. Cancer cells and specifically CRC cells were shown to change their source of lipids on the one hand by increasing extracellular uptake and on the other hand by reactivating de novo fatty acid synthesis regardless of extracellular lipid availability, providing them with metabolic flexibility and alternative sources of energy [ 12 , 42 , 45 ]. One source for scavenging extracellular lipids is adipocyte or hepatocyte-derived, plasma albumin-bound free-fatty acids.…”

Section: Lipid Biology In Crcmentioning

confidence: 99%

“…One report assessing matched biopsies showed no alterations in LDs [ 95 ] and yet other reports demonstrated decreased levels of triacylglycerol contents in tumor compared to paired adjacent tissue [ 89 ]. In turn they observed increased cell membrane components, namely phospho- and sphingolipids and argue that the conducted study analyzed specific lipids in much more detail, including mono-, diacylglycerols, lysophospholipids and ceramides and suggesting observed alterations of specific lipids depends on their role in either energy generation or cell membrane contribution [ 42 ]. A recent study also demonstrated a net decrease of TG in tumors, while showing altered composition inside LDs, evidenced by VLCFA increase compared to LCFA [ 96 ].…”

Section: Fatty Acid Storage and Degradationmentioning

confidence: 99%

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Lipid Metabolism Interplay in CRC—An Update

2022

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Colorectal cancer (CRC) to date still ranks as one of the deadliest cancer entities globally, and despite recent advances, the incidence in young adolescents is dramatically increasing. Lipid metabolism has recently received increased attention as a crucial element for multiple aspects of carcinogenesis and our knowledge of the underlying mechanisms is steadily growing. However, the mechanism how fatty acid metabolism contributes to CRC is still not understood in detail. In this review, we aim to summarize our vastly growing comprehension and the accompanied complexity of cellular fatty acid metabolism in CRC by describing inputs and outputs of intracellular free fatty acid pools and how these contribute to cancer initiation, disease progression and metastasis. We highlight how different lipid pathways can contribute to the aggressiveness of tumors and affect the prognosis of patients. Furthermore, we focus on the role of lipid metabolism in cell communication and interplay within the tumor microenvironment (TME) and beyond. Understanding these interactions in depth might lead to the discovery of novel markers and new therapeutic interventions for CRC. Finally, we discuss the crucial role of fatty acid metabolism as new targetable gatekeeper in colorectal cancer.

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Alterations in complex lipids in tumor tissue of patients with colorectal cancer

Cited by 17 publications

References 69 publications

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

Cell surface sphingomyelin: key role in cancer initiation, progression, and immune evasion

Reprogrammed Lipid Metabolism and the Lipid-Associated Hallmarks of Colorectal Cancer

Lipid Metabolism Interplay in CRC—An Update

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