ChloroquineV1, Ncbi, Merge, bibRecord, 000B58

Functions and Implications of Autophagy in Colon Cancer

Identifieur interne : 000B58 ( Ncbi/Merge ); précédent : 000B57; suivant : 000B59

Functions and Implications of Autophagy in Colon Cancer

Auteurs : Samantha N. Devenport [États-Unis] ; Yatrik M. Shah [États-Unis]

Source :

Cells [ 2073-4409 ] ; 2019.

RBID : PMC:6912527

Abstract

Autophagy is an essential function to breakdown cellular proteins and organelles to recycle for new nutrient building blocks. In colorectal cancer, the importance of autophagy is becoming widely recognized as it demonstrates both pro- and anti-tumorigenic functions. In colon cancer, cell autonomous and non-autonomous roles for autophagy are essential in growth and progression. However, the mechanisms downstream of autophagy (to reduce or enhance tumor growth) are not well known. Additionally, the signals that activate and coordinate autophagy for tumor cell growth and survival are not clear. Here, we highlight the context- and cargo-dependent role of autophagy in proliferation, cell death, and cargo breakdown.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912527

DOI: 10.3390/cells8111349
PubMed: 31671556
PubMed Central: 6912527

Links toward previous steps (curation, corpus...)

to stream Pmc, to step Corpus: 000928
to stream Pmc, to step Curation: 000928
to stream Pmc, to step Checkpoint: 000748

Links to Exploration step

PMC:6912527

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>Autophagy is an essential function to breakdown cellular proteins and organelles to recycle for new nutrient building blocks. In colorectal cancer, the importance of autophagy is becoming widely recognized as it demonstrates both pro- and anti-tumorigenic functions. In colon cancer, cell autonomous and non-autonomous roles for autophagy are essential in growth and progression. However, the mechanisms downstream of autophagy (to reduce or enhance tumor growth) are not well known. Additionally, the signals that activate and coordinate autophagy for tumor cell growth and survival are not clear. Here, we highlight the context- and cargo-dependent role of autophagy in proliferation, cell death, and cargo breakdown.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Cells</journal-id>
<journal-id journal-id-type="iso-abbrev">Cells</journal-id>
<journal-id journal-id-type="publisher-id">cells</journal-id>
<journal-title-group><journal-title>Cells</journal-title>
</journal-title-group>
<issn pub-type="epub">2073-4409</issn>
<publisher><publisher-name>MDPI</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31671556</article-id>
<article-id pub-id-type="pmc">6912527</article-id>
<article-id pub-id-type="doi">10.3390/cells8111349</article-id>
<article-id pub-id-type="publisher-id">cells-08-01349</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Functions and Implications of Autophagy in Colon Cancer</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Devenport</surname>
<given-names>Samantha N</given-names>
</name>
<xref ref-type="aff" rid="af1-cells-08-01349">1</xref>
<xref ref-type="aff" rid="af2-cells-08-01349">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Shah</surname>
<given-names>Yatrik M</given-names>
</name>
<xref ref-type="aff" rid="af1-cells-08-01349">1</xref>
<xref ref-type="aff" rid="af2-cells-08-01349">2</xref>
<xref rid="c1-cells-08-01349" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-cells-08-01349"><label>1</label>
Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA</aff>
<aff id="af2-cells-08-01349"><label>2</label>
Molecular and Integrative Physiology, Internal Medicine, Division of Gastroenterology, and Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA</aff>
<author-notes><corresp id="c1-cells-08-01349"><label>*</label>
Correspondence: <email>shahy@umich.edu</email>
; Tel.: +1-734-615-0567</corresp>
</author-notes>
<pub-date pub-type="epub"><day>30</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>11</month>
<year>2019</year>
</pub-date>
<volume>8</volume>
<issue>11</issue>
<elocation-id>1349</elocation-id>
<history><date date-type="received"><day>27</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>28</day>
<month>10</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>Autophagy is an essential function to breakdown cellular proteins and organelles to recycle for new nutrient building blocks. In colorectal cancer, the importance of autophagy is becoming widely recognized as it demonstrates both pro- and anti-tumorigenic functions. In colon cancer, cell autonomous and non-autonomous roles for autophagy are essential in growth and progression. However, the mechanisms downstream of autophagy (to reduce or enhance tumor growth) are not well known. Additionally, the signals that activate and coordinate autophagy for tumor cell growth and survival are not clear. Here, we highlight the context- and cargo-dependent role of autophagy in proliferation, cell death, and cargo breakdown.</p>
</abstract>
<kwd-group><kwd>autophagy</kwd>
<kwd>nutrient</kwd>
<kwd>cancer</kwd>
<kwd>colon</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="cells-08-01349-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Overview of autophagy subtypes; macro-autophagy, micro-autophagy, and CMA. Specifically, highlighting examples of selective macro-autophagy.</p>
</caption>
<graphic xlink:href="cells-08-01349-g001"></graphic>
</fig>
<fig id="cells-08-01349-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Schematic of the tumor microenvironment highlighting the impact of autophagy. Cell autonomous roles of autophagy in immune, epithelial or, the cross-talk between cell types in colorectal cancer.</p>
</caption>
<graphic xlink:href="cells-08-01349-g002"></graphic>
</fig>
<fig id="cells-08-01349-f003" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Schematic summarizing (<bold>A</bold>
) Simplified overview of mechanisms of mTORC1 regulation. and (<bold>B</bold>
) how nutrient modulation impacts autophagy. Bolded mechanisms indicate data from non-CRC samples. Please refer to text for detailed mechanisms.</p>
</caption>
<graphic xlink:href="cells-08-01349-g003"></graphic>
</fig>
<table-wrap id="cells-08-01349-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">cells-08-01349-t001_Table 1</object-id>
<label>Table 1</label>
<caption><p>Functions of autophagy in CRC. <bold>A</bold>
. Observation/Autophagy indicates what mechanisms are observed in CRC tumors and if autophagy is active or inactive. Tumor response is a summary of whether or not the autophagy activity indicated generates a pro- or anti- tumor response. <bold>B</bold>
. Summary of therapies and their modulation of autophagy. Treatment: Which therapy was employed. Autophagy: how the stated therapy modulated autophagy activation. Tumor response: how manipulation of autophagy via therapeutic treatment impacted tumor growth.</p>
</caption>
<table frame="hsides" rules="groups"><tbody><tr><td colspan="5" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1"><bold>A</bold>
</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Observation</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Autophagy</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Tumor response</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Reference</bold>
</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Activated chaperone-mediated autophagy in tumors</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B19-cells-08-01349" ref-type="bibr">19</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Epithelial mitophagy increases CD8+T-Cells</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B34-cells-08-01349" ref-type="bibr">34</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Loss of PARK2 accelerates tumor development</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B38-cells-08-01349" ref-type="bibr">38</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Decreased ATG5 in CRC patients</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B73-cells-08-01349" ref-type="bibr">73</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Increased ATG5 yields increased invasion</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B73-cells-08-01349" ref-type="bibr">73</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Active autophagy through LC3B and SQSTM1</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B74-cells-08-01349" ref-type="bibr">74</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Loss of ATG7</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B75-cells-08-01349" ref-type="bibr">75</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>RACK1 induces autophagy</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B76-cells-08-01349" ref-type="bibr">76</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>High Beclin-1 in CRC</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B80-cells-08-01349" ref-type="bibr">80</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Increased LC3 with loss of p53</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B81-cells-08-01349" ref-type="bibr">81</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Autophagy suppresses immune response in KRAS cancer</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B82-cells-08-01349" ref-type="bibr">82</xref>
]</td>
</tr>
<tr><td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Autophagy drives glycolysis in RAS cancers</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pro-tumor</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B83-cells-08-01349" ref-type="bibr">83</xref>
]</td>
</tr>
<tr><td colspan="5" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>B</bold>
</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Treatment</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Autophagy</bold>
</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1"><bold>Tumor response</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Reference</bold>
</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Mito-CP or Mito-Met10</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Decreased proliferation in KRAS mutant cancers.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B47-cells-08-01349" ref-type="bibr">47</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>BH3 mimetic and chloroquine</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Induced apoptosis.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B48-cells-08-01349" ref-type="bibr">48</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Bafilomycin A1 or chloroquine</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Elevated FOXO3a and transcriptional upregulation of pro-apoptotic genes.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B77-cells-08-01349" ref-type="bibr">77</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Brevlin A</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Promoted expression of LC3-II and induced autophagy.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B79-cells-08-01349" ref-type="bibr">79</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>KRAS siRNA</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Inhibiting mutant Kras inhibits autophagy and induces apoptosis.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B84-cells-08-01349" ref-type="bibr">84</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Vorinostat with chloroquine</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Induced apoptosis.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B85-cells-08-01349" ref-type="bibr">85</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>5-Fuorouracil and chloroquine</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Inactive</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; 5-FU treatment induced autophagy for resistance. Inhibition of autophagy reduced growth.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B86-cells-08-01349" ref-type="bibr">86</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Temsirolimus</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Inhibited mTOR to activate autophagy and degrade CIP2A.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B87-cells-08-01349" ref-type="bibr">87</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Estrogen Receptor Beta</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Autophagy directed CyclinD1 degradation inhibited growth.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B88-cells-08-01349" ref-type="bibr">88</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>4-Hydroxytamoxifen</bold>
</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Active</td>
<td colspan="2" align="center" valign="middle" style="border-bottom:solid thin" rowspan="1">Anti-Tumor; Degradation of KRAS through autophagy induced cel death.</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B89-cells-08-01349" ref-type="bibr">89</xref>
]</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Devenport, Samantha N" sort="Devenport, Samantha N" uniqKey="Devenport S" first="Samantha N" last="Devenport">Samantha N. Devenport</name>
</noRegion>
<name sortKey="Devenport, Samantha N" sort="Devenport, Samantha N" uniqKey="Devenport S" first="Samantha N" last="Devenport">Samantha N. Devenport</name>
<name sortKey="Shah, Yatrik M" sort="Shah, Yatrik M" uniqKey="Shah Y" first="Yatrik M" last="Shah">Yatrik M. Shah</name>
<name sortKey="Shah, Yatrik M" sort="Shah, Yatrik M" uniqKey="Shah Y" first="Yatrik M" last="Shah">Yatrik M. Shah</name>
</country>
</tree>
</affiliations>
</record>

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Functions and Implications of Autophagy in Colon Cancer

Functions and Implications of Autophagy in Colon Cancer

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