PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer
Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collecte...
Gespeichert in:
| Veröffentlicht in: | Cell death & disease 2018-07, Vol.9 (7), p.739-11, Article 739 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 11 |
|---|---|
| container_issue | 7 |
| container_start_page | 739 |
| container_title | Cell death & disease |
| container_volume | 9 |
| creator | Wang, Qiang Shi, Yan-long Zhou, Kai Wang, Li-li Yan, Ze-xuan Liu, Yu-lin Xu, Li-li Zhao, Shi-wei Chu, Hui-li Shi, Ting-ting Ma, Qing-hua Bi, Jingwang |
| description | Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the
PIK3CA
gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with
PIK3A
mutation showed worse response to first-line chemotherapy than those without
PIK3CA
mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5
+
CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore,
PIK3CA
mutation
/LGR5
+
expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA
mutation
/LGR5
+
expression was a potential biomarker for monitoring chemotherapy resistance in CRC. |
| doi_str_mv | 10.1038/s41419-018-0776-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6030128</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2063688556</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-d54b09bcb22b2edaac3bc2be2a9e8fb8db0f6270b1bfe11cb999cf569866c7803</originalsourceid><addsrcrecordid>eNp1kV1LHDEUhoNUVOz-gN7IQG96MzYfM5nkpiBL_aBCRex1SLJn3MhMsk0yBf-9GVZXK5ibBM5z3pPDg9AXgk8JZuJ7akhDZI2JqHHX8ZrvoSOKG1I3QshPb96HaJHSAy6HMUxbfoAOqZQdFpIeodubq19seVaNU9bZBZ8qG3wPsYqQXMraW6hyqHoXU64H56GyaxhDXkPUm8fK-cIPIYLNeqjsjMfPaL_XQ4LF832M_pz_vFte1te_L66WZ9e1bRnP9aptDJbGGkoNhZXWlhlLDVAtQfRGrAzuOe2wIaYHQqyRUtq-5VJwbjuB2TH6sc3dTGaElQWfox7UJrpRx0cVtFP_V7xbq_vwT3HMMKGiBHx7Dojh7wQpq9ElC8OgPYQpKYp5Q5nsSFvQr-_QhzBFX9abKcaFaFteKLKlbAwpReh3nyFYzdLUVpoq0tQsTc09J2-32HW8KCoA3QKplPw9xNfRH6c-ARX2o68</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2063688556</pqid></control><display><type>article</type><title>PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Wang, Qiang ; Shi, Yan-long ; Zhou, Kai ; Wang, Li-li ; Yan, Ze-xuan ; Liu, Yu-lin ; Xu, Li-li ; Zhao, Shi-wei ; Chu, Hui-li ; Shi, Ting-ting ; Ma, Qing-hua ; Bi, Jingwang</creator><creatorcontrib>Wang, Qiang ; Shi, Yan-long ; Zhou, Kai ; Wang, Li-li ; Yan, Ze-xuan ; Liu, Yu-lin ; Xu, Li-li ; Zhao, Shi-wei ; Chu, Hui-li ; Shi, Ting-ting ; Ma, Qing-hua ; Bi, Jingwang</creatorcontrib><description>Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the
PIK3CA
gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with
PIK3A
mutation showed worse response to first-line chemotherapy than those without
PIK3CA
mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5
+
CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore,
PIK3CA
mutation
/LGR5
+
expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA
mutation
/LGR5
+
expression was a potential biomarker for monitoring chemotherapy resistance in CRC.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-018-0776-6</identifier><identifier>PMID: 29970892</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>1-Phosphatidylinositol 3-kinase ; 38/1 ; 38/70 ; 96/100 ; Adult ; Aged ; Aged, 80 and over ; AKT protein ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell proliferation ; Cell Survival - drug effects ; Chemoresistance ; Chemotherapy ; Chromones - pharmacology ; Class I Phosphatidylinositol 3-Kinases - genetics ; Class I Phosphatidylinositol 3-Kinases - metabolism ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Female ; Fluorouracil - therapeutic use ; HCT116 Cells ; Humans ; Immunology ; Life Sciences ; Male ; Medical records ; Middle Aged ; Morpholines - pharmacology ; Multivariate Analysis ; Mutation ; Mutation - genetics ; Patients ; Phosphorylcholine - analogs & derivatives ; Phosphorylcholine - pharmacology ; Receptors, G-Protein-Coupled - genetics ; Receptors, G-Protein-Coupled - metabolism ; Retrospective Studies ; Stem cells ; Tumor cells</subject><ispartof>Cell death & disease, 2018-07, Vol.9 (7), p.739-11, Article 739</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-d54b09bcb22b2edaac3bc2be2a9e8fb8db0f6270b1bfe11cb999cf569866c7803</citedby><cites>FETCH-LOGICAL-c536t-d54b09bcb22b2edaac3bc2be2a9e8fb8db0f6270b1bfe11cb999cf569866c7803</cites><orcidid>0000-0003-2614-9201</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030128/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030128/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29970892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Shi, Yan-long</creatorcontrib><creatorcontrib>Zhou, Kai</creatorcontrib><creatorcontrib>Wang, Li-li</creatorcontrib><creatorcontrib>Yan, Ze-xuan</creatorcontrib><creatorcontrib>Liu, Yu-lin</creatorcontrib><creatorcontrib>Xu, Li-li</creatorcontrib><creatorcontrib>Zhao, Shi-wei</creatorcontrib><creatorcontrib>Chu, Hui-li</creatorcontrib><creatorcontrib>Shi, Ting-ting</creatorcontrib><creatorcontrib>Ma, Qing-hua</creatorcontrib><creatorcontrib>Bi, Jingwang</creatorcontrib><title>PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the
PIK3CA
gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with
PIK3A
mutation showed worse response to first-line chemotherapy than those without
PIK3CA
mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5
+
CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore,
PIK3CA
mutation
/LGR5
+
expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA
mutation
/LGR5
+
expression was a potential biomarker for monitoring chemotherapy resistance in CRC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>38/1</subject><subject>38/70</subject><subject>96/100</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell proliferation</subject><subject>Cell Survival - drug effects</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Chromones - pharmacology</subject><subject>Class I Phosphatidylinositol 3-Kinases - genetics</subject><subject>Class I Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Female</subject><subject>Fluorouracil - therapeutic use</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical records</subject><subject>Middle Aged</subject><subject>Morpholines - pharmacology</subject><subject>Multivariate Analysis</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Patients</subject><subject>Phosphorylcholine - analogs & derivatives</subject><subject>Phosphorylcholine - pharmacology</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Retrospective Studies</subject><subject>Stem cells</subject><subject>Tumor cells</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kV1LHDEUhoNUVOz-gN7IQG96MzYfM5nkpiBL_aBCRex1SLJn3MhMsk0yBf-9GVZXK5ibBM5z3pPDg9AXgk8JZuJ7akhDZI2JqHHX8ZrvoSOKG1I3QshPb96HaJHSAy6HMUxbfoAOqZQdFpIeodubq19seVaNU9bZBZ8qG3wPsYqQXMraW6hyqHoXU64H56GyaxhDXkPUm8fK-cIPIYLNeqjsjMfPaL_XQ4LF832M_pz_vFte1te_L66WZ9e1bRnP9aptDJbGGkoNhZXWlhlLDVAtQfRGrAzuOe2wIaYHQqyRUtq-5VJwbjuB2TH6sc3dTGaElQWfox7UJrpRx0cVtFP_V7xbq_vwT3HMMKGiBHx7Dojh7wQpq9ElC8OgPYQpKYp5Q5nsSFvQr-_QhzBFX9abKcaFaFteKLKlbAwpReh3nyFYzdLUVpoq0tQsTc09J2-32HW8KCoA3QKplPw9xNfRH6c-ARX2o68</recordid><startdate>20180703</startdate><enddate>20180703</enddate><creator>Wang, Qiang</creator><creator>Shi, Yan-long</creator><creator>Zhou, Kai</creator><creator>Wang, Li-li</creator><creator>Yan, Ze-xuan</creator><creator>Liu, Yu-lin</creator><creator>Xu, Li-li</creator><creator>Zhao, Shi-wei</creator><creator>Chu, Hui-li</creator><creator>Shi, Ting-ting</creator><creator>Ma, Qing-hua</creator><creator>Bi, Jingwang</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PKEHL</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2614-9201</orcidid></search><sort><creationdate>20180703</creationdate><title>PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer</title><author>Wang, Qiang ; Shi, Yan-long ; Zhou, Kai ; Wang, Li-li ; Yan, Ze-xuan ; Liu, Yu-lin ; Xu, Li-li ; Zhao, Shi-wei ; Chu, Hui-li ; Shi, Ting-ting ; Ma, Qing-hua ; Bi, Jingwang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-d54b09bcb22b2edaac3bc2be2a9e8fb8db0f6270b1bfe11cb999cf569866c7803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>38/1</topic><topic>38/70</topic><topic>96/100</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>AKT protein</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell proliferation</topic><topic>Cell Survival - drug effects</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Chromones - pharmacology</topic><topic>Class I Phosphatidylinositol 3-Kinases - genetics</topic><topic>Class I Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Female</topic><topic>Fluorouracil - therapeutic use</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical records</topic><topic>Middle Aged</topic><topic>Morpholines - pharmacology</topic><topic>Multivariate Analysis</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Patients</topic><topic>Phosphorylcholine - analogs & derivatives</topic><topic>Phosphorylcholine - pharmacology</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Retrospective Studies</topic><topic>Stem cells</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Shi, Yan-long</creatorcontrib><creatorcontrib>Zhou, Kai</creatorcontrib><creatorcontrib>Wang, Li-li</creatorcontrib><creatorcontrib>Yan, Ze-xuan</creatorcontrib><creatorcontrib>Liu, Yu-lin</creatorcontrib><creatorcontrib>Xu, Li-li</creatorcontrib><creatorcontrib>Zhao, Shi-wei</creatorcontrib><creatorcontrib>Chu, Hui-li</creatorcontrib><creatorcontrib>Shi, Ting-ting</creatorcontrib><creatorcontrib>Ma, Qing-hua</creatorcontrib><creatorcontrib>Bi, Jingwang</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Qiang</au><au>Shi, Yan-long</au><au>Zhou, Kai</au><au>Wang, Li-li</au><au>Yan, Ze-xuan</au><au>Liu, Yu-lin</au><au>Xu, Li-li</au><au>Zhao, Shi-wei</au><au>Chu, Hui-li</au><au>Shi, Ting-ting</au><au>Ma, Qing-hua</au><au>Bi, Jingwang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2018-07-03</date><risdate>2018</risdate><volume>9</volume><issue>7</issue><spage>739</spage><epage>11</epage><pages>739-11</pages><artnum>739</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Chemotherapy represents an important treatment option for colorectal cancer (CRC), but only half of the patients benefit from these regimens. We explored the potential predicting value and mechanism of PIK3CA mutation in CRC chemotherapy. CRC specimens from 440 patients were retrospectively collected and examined with a fluorescence PCR-based method. The correlation of first-line chemotherapy response and PIK3CA mutation was evaluated according to follow-up and medical records. The underlying mechanism of PIK3CA mutation in chemotherapy resistance was assessed with CRC tumors and primary cells. The mutation frequency of the
PIK3CA
gene in CRC patients was 9.55%, which was correlated with late TNM staging and lower histological grade. The CRC patients with
PIK3A
mutation showed worse response to first-line chemotherapy than those without
PIK3CA
mutation. PIK3A mutation tumor cells showed poor sensitivity to first-line chemotherapy in vitro and in vivo. PIK3CA mutation induced PI3K/Akt signaling activation to increase LGR5
+
CRC stem cells survival and proliferation, from which lead to chemotherapy resistance. Furthermore,
PIK3CA
mutation
/LGR5
+
expression was an independent detrimental factor for CRC patients. Our findings indicated that PIK3CA mutation induced PI3K/Akt activation contributed to CRC stem cells survival and proliferation, from which cells further resistance to chemotherapy. PIK3CA
mutation
/LGR5
+
expression was a potential biomarker for monitoring chemotherapy resistance in CRC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29970892</pmid><doi>10.1038/s41419-018-0776-6</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2614-9201</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-4889 |
| ispartof | Cell death & disease, 2018-07, Vol.9 (7), p.739-11, Article 739 |
| issn | 2041-4889 2041-4889 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6030128 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | 1-Phosphatidylinositol 3-kinase 38/1 38/70 96/100 Adult Aged Aged, 80 and over AKT protein Antibodies Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell proliferation Cell Survival - drug effects Chemoresistance Chemotherapy Chromones - pharmacology Class I Phosphatidylinositol 3-Kinases - genetics Class I Phosphatidylinositol 3-Kinases - metabolism Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Female Fluorouracil - therapeutic use HCT116 Cells Humans Immunology Life Sciences Male Medical records Middle Aged Morpholines - pharmacology Multivariate Analysis Mutation Mutation - genetics Patients Phosphorylcholine - analogs & derivatives Phosphorylcholine - pharmacology Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Retrospective Studies Stem cells Tumor cells |
| title | PIK3CA mutations confer resistance to first-line chemotherapy in colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A23%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PIK3CA%20mutations%20confer%20resistance%20to%20first-line%20chemotherapy%20in%20colorectal%20cancer&rft.jtitle=Cell%20death%20&%20disease&rft.au=Wang,%20Qiang&rft.date=2018-07-03&rft.volume=9&rft.issue=7&rft.spage=739&rft.epage=11&rft.pages=739-11&rft.artnum=739&rft.issn=2041-4889&rft.eissn=2041-4889&rft_id=info:doi/10.1038/s41419-018-0776-6&rft_dat=%3Cproquest_pubme%3E2063688556%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2063688556&rft_id=info:pmid/29970892&rfr_iscdi=true |