Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance
Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER + ) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated...
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| Veröffentlicht in: | Science China. Life sciences 2024-07, Vol.67 (7), p.1413-1426 |
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| container_title | Science China. Life sciences |
| container_volume | 67 |
| creator | Chen, Xueyan Wu, Weilin Jeong, Ji-Hak Rokavec, Matjaz Wei, Rui Feng, Shaolong Schroth, Werner Brauch, Hiltrud Zhong, Shangwei Luo, Jun-Li |
| description | Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER
+
) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER
+
breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER
+
human breast cancer was correlated with lymphotoxin β (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER
+
breast cancer. |
| doi_str_mv | 10.1007/s11427-023-2460-0 |
| format | Article |
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+
) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER
+
breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER
+
human breast cancer was correlated with lymphotoxin β (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER
+
breast cancer.</description><identifier>ISSN: 1674-7305</identifier><identifier>ISSN: 1869-1889</identifier><identifier>EISSN: 1869-1889</identifier><identifier>DOI: 10.1007/s11427-023-2460-0</identifier><identifier>PMID: 38565741</identifier><language>eng</language><publisher>Beijing: Science China Press</publisher><subject>Biomedical and Life Sciences ; Breast cancer ; Cytokines ; Endocrine therapy ; Estrogen receptors ; Estrogens ; Life Sciences ; Lymphotoxin ; Metastases ; Pax5 protein ; Research Paper ; Tamoxifen ; Therapeutic targets</subject><ispartof>Science China. Life sciences, 2024-07, Vol.67 (7), p.1413-1426</ispartof><rights>Science China Press 2024</rights><rights>2024. Science China Press.</rights><rights>Science China Press 2024.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c324t-8b7bb3e211a7213f35e0ba26932426c0dda167043142dabdf8c9b73e0786c8483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11427-023-2460-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11427-023-2460-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38565741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xueyan</creatorcontrib><creatorcontrib>Wu, Weilin</creatorcontrib><creatorcontrib>Jeong, Ji-Hak</creatorcontrib><creatorcontrib>Rokavec, Matjaz</creatorcontrib><creatorcontrib>Wei, Rui</creatorcontrib><creatorcontrib>Feng, Shaolong</creatorcontrib><creatorcontrib>Schroth, Werner</creatorcontrib><creatorcontrib>Brauch, Hiltrud</creatorcontrib><creatorcontrib>Zhong, Shangwei</creatorcontrib><creatorcontrib>Luo, Jun-Li</creatorcontrib><title>Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance</title><title>Science China. Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER
+
) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER
+
breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER
+
human breast cancer was correlated with lymphotoxin β (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER
+
breast cancer.</description><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Cytokines</subject><subject>Endocrine therapy</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Life Sciences</subject><subject>Lymphotoxin</subject><subject>Metastases</subject><subject>Pax5 protein</subject><subject>Research Paper</subject><subject>Tamoxifen</subject><subject>Therapeutic targets</subject><issn>1674-7305</issn><issn>1869-1889</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kMtOxCAUhonRqFEfwI1p4sYNeoAW6NJMvEUTN7pxQyg91epMOwJV57F8EZ9JmvGSmMgGwvn4D-cjZJfBIQNQR4GxnCsKXFCeS6CwQjaZliVlWper6SxVTpWAYoPshPAIaQkBXKl1siF0IQuVs01yN1nE_qntMFDrYvtiI9ZZN7gpWp9dXF5-vNPT4xsG2dzGh1e7yNquHhyGrPJoQ8yc7Rz6LNpZ_9Y22FGPoQ1xvN0ma42dBtz52rfI7enJzeScXl2fXUyOr6gTPI9UV6qqBHLGrOJMNKJAqCyXZapy6aCubRoFcpHGrW1VN9qVlRIISkuncy22yMEyd-775wFDNLM2OJxObYf9EIwAwaRkrISE7v9BH_vBd-l3iZJlUSilxkC2pJzvQ_DYmLlvZ9YvDAMzujdL9ya5N6N7MybvfSUP1QzrnxffphPAl0BIpe4e_W_r_1M_AYKjjeo</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Chen, Xueyan</creator><creator>Wu, Weilin</creator><creator>Jeong, Ji-Hak</creator><creator>Rokavec, Matjaz</creator><creator>Wei, Rui</creator><creator>Feng, Shaolong</creator><creator>Schroth, Werner</creator><creator>Brauch, Hiltrud</creator><creator>Zhong, Shangwei</creator><creator>Luo, Jun-Li</creator><general>Science China Press</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20240701</creationdate><title>Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance</title><author>Chen, Xueyan ; Wu, Weilin ; Jeong, Ji-Hak ; Rokavec, Matjaz ; Wei, Rui ; Feng, Shaolong ; Schroth, Werner ; Brauch, Hiltrud ; Zhong, Shangwei ; Luo, Jun-Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c324t-8b7bb3e211a7213f35e0ba26932426c0dda167043142dabdf8c9b73e0786c8483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Cytokines</topic><topic>Endocrine therapy</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Life Sciences</topic><topic>Lymphotoxin</topic><topic>Metastases</topic><topic>Pax5 protein</topic><topic>Research Paper</topic><topic>Tamoxifen</topic><topic>Therapeutic targets</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xueyan</creatorcontrib><creatorcontrib>Wu, Weilin</creatorcontrib><creatorcontrib>Jeong, Ji-Hak</creatorcontrib><creatorcontrib>Rokavec, Matjaz</creatorcontrib><creatorcontrib>Wei, Rui</creatorcontrib><creatorcontrib>Feng, Shaolong</creatorcontrib><creatorcontrib>Schroth, Werner</creatorcontrib><creatorcontrib>Brauch, Hiltrud</creatorcontrib><creatorcontrib>Zhong, Shangwei</creatorcontrib><creatorcontrib>Luo, Jun-Li</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Science China. Life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xueyan</au><au>Wu, Weilin</au><au>Jeong, Ji-Hak</au><au>Rokavec, Matjaz</au><au>Wei, Rui</au><au>Feng, Shaolong</au><au>Schroth, Werner</au><au>Brauch, Hiltrud</au><au>Zhong, Shangwei</au><au>Luo, Jun-Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance</atitle><jtitle>Science China. Life sciences</jtitle><stitle>Sci. China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>67</volume><issue>7</issue><spage>1413</spage><epage>1426</epage><pages>1413-1426</pages><issn>1674-7305</issn><issn>1869-1889</issn><eissn>1869-1889</eissn><abstract>Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER
+
) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER
+
breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER
+
human breast cancer was correlated with lymphotoxin β (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER
+
breast cancer.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>38565741</pmid><doi>10.1007/s11427-023-2460-0</doi><tpages>14</tpages></addata></record> |
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| subjects | Biomedical and Life Sciences Breast cancer Cytokines Endocrine therapy Estrogen receptors Estrogens Life Sciences Lymphotoxin Metastases Pax5 protein Research Paper Tamoxifen Therapeutic targets |
| title | Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance |
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