Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer
Identifieur interne : 000781 ( Ncbi/Merge ); précédent : 000780; suivant : 000782Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer
Auteurs : Zuzanna Tracz-Gaszewska ; Pawel DobrzynSource :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.
Url:
DOI: 10.3390/cancers11070948
PubMed: 31284458
PubMed Central: 6678606
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer</title><author><name sortKey="Tracz Gaszewska, Zuzanna" sort="Tracz Gaszewska, Zuzanna" uniqKey="Tracz Gaszewska Z" first="Zuzanna" last="Tracz-Gaszewska">Zuzanna Tracz-Gaszewska</name></author><author><name sortKey="Dobrzyn, Pawel" sort="Dobrzyn, Pawel" uniqKey="Dobrzyn P" first="Pawel" last="Dobrzyn">Pawel Dobrzyn</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31284458</idno><idno type="pmc">6678606</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678606</idno><idno type="RBID">PMC:6678606</idno><idno type="doi">10.3390/cancers11070948</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000891</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000891</idno><idno type="wicri:Area/Pmc/Curation">000891</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000891</idno><idno type="wicri:Area/Pmc/Checkpoint">000382</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000382</idno><idno type="wicri:Area/Ncbi/Merge">000781</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer</title><author><name sortKey="Tracz Gaszewska, Zuzanna" sort="Tracz Gaszewska, Zuzanna" uniqKey="Tracz Gaszewska Z" first="Zuzanna" last="Tracz-Gaszewska">Zuzanna Tracz-Gaszewska</name></author><author><name sortKey="Dobrzyn, Pawel" sort="Dobrzyn, Pawel" uniqKey="Dobrzyn P" first="Pawel" last="Dobrzyn">Pawel Dobrzyn</name></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Warburg, O" uniqKey="Warburg O">O. Warburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warburg, O" uniqKey="Warburg O">O. Warburg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rohrig, F" uniqKey="Rohrig F">F. Röhrig</name></author><author><name sortKey="Schulze, A" uniqKey="Schulze A">A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cancers (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Cancers (Basel)</journal-id><journal-id journal-id-type="publisher-id">cancers</journal-id><journal-title-group><journal-title>Cancers</journal-title></journal-title-group><issn pub-type="epub">2072-6694</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31284458</article-id><article-id pub-id-type="pmc">6678606</article-id><article-id pub-id-type="doi">10.3390/cancers11070948</article-id><article-id pub-id-type="publisher-id">cancers-11-00948</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tracz-Gaszewska</surname><given-names>Zuzanna</given-names></name></contrib><contrib contrib-type="author"><name><surname>Dobrzyn</surname><given-names>Pawel</given-names></name><xref rid="c1-cancers-11-00948" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-cancers-11-00948">Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology Polish Academy of Sciences, 02-093 Warsaw, Poland</aff><author-notes><corresp id="c1-cancers-11-00948"><label>*</label>Correspondence: <email>p.dobrzyn@nencki.gov.pl</email></corresp></author-notes><pub-date pub-type="epub"><day>05</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>7</month><year>2019</year></pub-date><volume>11</volume><issue>7</issue><elocation-id>948</elocation-id><history><date date-type="received"><day>05</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>03</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.</p></abstract><kwd-group><kwd>lipid metabolism</kwd><kwd>stearoyl-CoA desaturase 1 (SCD1)</kwd><kwd>monounsaturated fatty acids</kwd><kwd>SCD1 inhibitors</kwd><kwd>targeted therapy</kwd></kwd-group></article-meta></front><floats-group><fig id="cancers-11-00948-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Stearoyl-CoA desaturase 1 (SCD1) as a molecular target for anticancer therapy. SCD1 inhibitors suppress cancer cell proliferation, tumor formation and growth, and cancer cell migration, invasion, metastasis, and stemness. SCD1 regulates these tumorigenic events indirectly through monounsaturated fatty acids (MUFA) synthesis or directly by modulating various signaling pathways (e.g., epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) mitogenic pathway, AKT/GSKβ/β-catenin pathway for stimulation of the epithelial–mesenchymal transition, and Wnt/β-catenin/Hippo pathway for the maintenance of cancer cell stemness). Red arrows indicate the anticancer effect of SCD1 inhibition.</p></caption><graphic xlink:href="cancers-11-00948-g001"></graphic></fig><table-wrap id="cancers-11-00948-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cancers-11-00948-t001_Table 1</object-id><label>Table 1</label><caption><p>Stearoyl-CoA desaturase 1 inhibitors with anticancer activity.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Inhibitor Name</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Activity in Vitro</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Activity in Vivo</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Side Effects</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">A939572</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation and induces the apoptosis of lung, pharynx, renal, bladder, liver, colorectal, thyroid, and endometrial cancer cells.<break></break>Suppresses the migration and invasion of hepatocellular carcinoma cells and breast cancer cells.<break></break>Impairs the migration of breast cancer cells that is driven by cancer-associated fibroblasts.<break></break>Effectively inhibits the proliferation and colony formation of clear cell renal cell carcinoma cells in combination with temsirolimus.<break></break>Sensitizes glioblastoma cells to temozolomide treatment.<break></break>Combined administration with bortezomib or carfilzomib impairs the proliferation and induces the apoptosis of anaplastic thyroid carcinoma cells.<break></break>Impairs the self-renewal, invasiveness, and sorafenib resistance of hepatocellular carcinoma stem cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Suppresses the growth of gastric and colorectal cancer xenografts in mice.<break></break>Combined treatment with temsirolimus effectively inhibits the growth of clear cell renal cell carcinoma xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mucosal discharge from eyes and increase in squinting.<break></break>Hair loss, eye ptosis, and sebaceous gland atrophy.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B27-cancers-11-00948" ref-type="bibr">27</xref>,<xref rid="B60-cancers-11-00948" ref-type="bibr">60</xref>,<xref rid="B64-cancers-11-00948" ref-type="bibr">64</xref>,<xref rid="B71-cancers-11-00948" ref-type="bibr">71</xref>,<xref rid="B72-cancers-11-00948" ref-type="bibr">72</xref>,<xref rid="B73-cancers-11-00948" ref-type="bibr">73</xref>,<xref rid="B74-cancers-11-00948" ref-type="bibr">74</xref>,<xref rid="B75-cancers-11-00948" ref-type="bibr">75</xref>,<xref rid="B84-cancers-11-00948" ref-type="bibr">84</xref>,<xref rid="B85-cancers-11-00948" ref-type="bibr">85</xref>,<xref rid="B86-cancers-11-00948" ref-type="bibr">86</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MF-438</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation and induces the apoptosis of breast cancer cells.<break></break>Combined administration with bortezomib or carfilzomib impairs the proliferation and induces the apoptosis of anaplastic thyroid carcinoma cells.<break></break>Reverses the resistance of stem-like non-small cell lung cancer cells to cisplatin and melanoma spheroids to B-Raf proto-oncogene, serine/threonine kinase/ mitogen-activated protein kinase kinase (BRAF/MEK) inhibitors.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Combined treatment with carfilzomib suppresses the growth of anaplastic thyroid carcinoma xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mucosal discharge from eyes and increase in squinting.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B27-cancers-11-00948" ref-type="bibr">27</xref>,<xref rid="B77-cancers-11-00948" ref-type="bibr">77</xref>,<xref rid="B87-cancers-11-00948" ref-type="bibr">87</xref>,<xref rid="B88-cancers-11-00948" ref-type="bibr">88</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CVT-11127</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation and induces the apoptosis of non-small cell lung cancer cells and breast cancer cells.<break></break>Potentiates the gefitinib-dependent inhibition of non-small cell lung cancer cell proliferation.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B76-cancers-11-00948" ref-type="bibr">76</xref>,<xref rid="B78-cancers-11-00948" ref-type="bibr">78</xref>,<xref rid="B79-cancers-11-00948" ref-type="bibr">79</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CVT-12012</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Potentiates the gefitinib-dependent inhibition of non-small cell lung cancer cell proliferation.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B79-cancers-11-00948" ref-type="bibr">79</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CAY10566</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation and induces the apoptosis of colorectal cancer cells.<break></break>Induces the apoptosis of hepatocellular carcinoma cells.<break></break>Inhibits the proliferation of ovarian cancer stem cells grown in spheroids.<break></break>Impairs the stemness of ovarian cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Suppresses lung metastasis and prolongs the overall survival of mice that are injected with co-cultured murine melanoma cancer cells and murine lung fibroblasts.<break></break>Suppresses the formation of tumors by ovarian cancer stem cells in mice.<break></break>Suppresses the growth of glioma stem-like xenograft in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B19-cancers-11-00948" ref-type="bibr">19</xref>,<xref rid="B29-cancers-11-00948" ref-type="bibr">29</xref>,<xref rid="B74-cancers-11-00948" ref-type="bibr">74</xref>,<xref rid="B89-cancers-11-00948" ref-type="bibr">89</xref>,<xref rid="B90-cancers-11-00948" ref-type="bibr">90</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">T-3764518</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation and induces the apoptosis of colorectal cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Suppresses the growth of colorectal, mesothelioma, and renal cell adenocarcinoma xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Reduces toxicity in a mouse model.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B82-cancers-11-00948" ref-type="bibr">82</xref>,<xref rid="B83-cancers-11-00948" ref-type="bibr">83</xref>,<xref rid="B91-cancers-11-00948" ref-type="bibr">91</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">BZ36</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Inhibits the proliferation of prostate cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Suppresses the growth of gastric and prostate cancer xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B81-cancers-11-00948" ref-type="bibr">81</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SSI-4</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Impairs the proliferation of a broad range of cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Reduces the growth of hepatocellular carcinoma xenografts in mice and enhances sorafenib toxicity with combined treatment.<break></break>Suppresses the growth of clear cell renal cell carcinoma xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B73-cancers-11-00948" ref-type="bibr">73</xref>,<xref rid="B92-cancers-11-00948" ref-type="bibr">92</xref>,<xref rid="B93-cancers-11-00948" ref-type="bibr">93</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SW208108</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Induces the apoptosis of non-small cell lung cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-drug does not affect sebocytes.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B94-cancers-11-00948" ref-type="bibr">94</xref>,<xref rid="B95-cancers-11-00948" ref-type="bibr">95</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SW203668</td><td valign="middle" style="border-bottom:solid thin" align="left" rowspan="1" colspan="1">Induces the apoptosis of non-small cell lung cancer cells.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Suppresses the growth of non-small cell lung cancer xenografts in mice.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-drug does not affect sebocytes.</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B94-cancers-11-00948" ref-type="bibr">94</xref>,<xref rid="B95-cancers-11-00948" ref-type="bibr">95</xref>]</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Dobrzyn, Pawel" sort="Dobrzyn, Pawel" uniqKey="Dobrzyn P" first="Pawel" last="Dobrzyn">Pawel Dobrzyn</name><name sortKey="Tracz Gaszewska, Zuzanna" sort="Tracz Gaszewska, Zuzanna" uniqKey="Tracz Gaszewska Z" first="Zuzanna" last="Tracz-Gaszewska">Zuzanna Tracz-Gaszewska</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|clé= PMC:6678606
|texte= Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:31284458" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |