Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia
Abstract Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). PACSIN2, a novel Cobll1 binding protein, activates TKI‐induced apoptosis in K562 cells, and this activation is suppressed by Cobll1 through the interaction between...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4727 |
| _version_ | 1811328227023519744 |
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| author | Kibeom Park Hee‐Seop Yoo Chang‐Kyu Oh Joo Rak Lee Hee Jin Chung Ha‐Neul Kim Soo‐Hyun Kim Kyung‐Mi Kee Tong Yoon Kim Myungshin Kim Byung‐Gyu Kim Jae Sun Ra Kyungjae Myung Hongtae Kim Seung Hun Han Min‐Duk Seo Yoonsung Lee Dong‐Wook Kim |
| author_facet | Kibeom Park Hee‐Seop Yoo Chang‐Kyu Oh Joo Rak Lee Hee Jin Chung Ha‐Neul Kim Soo‐Hyun Kim Kyung‐Mi Kee Tong Yoon Kim Myungshin Kim Byung‐Gyu Kim Jae Sun Ra Kyungjae Myung Hongtae Kim Seung Hun Han Min‐Duk Seo Yoonsung Lee Dong‐Wook Kim |
| author_sort | Kibeom Park |
| collection | DOAJ |
| description | Abstract Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). PACSIN2, a novel Cobll1 binding protein, activates TKI‐induced apoptosis in K562 cells, and this activation is suppressed by Cobll1 through the interaction between PACSIN2 and Cobll1. PACSIN2 also binds and inhibits SH3BP1 which activates the downstream Rac1 pathway and induces TKI resistance. PACSIN2 competitively interacts with Cobll1 or SH3BP1 with a higher affinity for Cobll1. Cobll1 preferentially binds to PACSIN2, releasing SH3BP1 to promote the SH3BP1/Rac1 pathway and suppress TKI‐mediated apoptosis and eventually leading to TKI resistance. Similar interactions among Cobll1, PACSIN2, and SH3BP1 control hematopoiesis during vertebrate embryogenesis. Clinical analysis showed that most patients with CML have Cobll1 and SH3BP1 expression at the BC phase and BC patients with Cobll1 and SH3BP1 expression showed severe progression with a higher blast percentage than those without any Cobll1, PACSIN2, or SH3BP1 expression. Our study details the molecular mechanism of the Cobll1/PACSIN2/SH3BP1 pathway in regulating drug resistance and BC progression in CML. |
| first_indexed | 2024-04-13T15:21:28Z |
| format | Article |
| id | doaj.art-b46d4d333a56496f9e49e9161fbe2a8e |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-13T15:21:28Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-b46d4d333a56496f9e49e9161fbe2a8e2022-12-22T02:41:39ZengWileyCancer Medicine2045-76342022-11-0111214005402010.1002/cam4.4727Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemiaKibeom Park0Hee‐Seop Yoo1Chang‐Kyu Oh2Joo Rak Lee3Hee Jin Chung4Ha‐Neul Kim5Soo‐Hyun Kim6Kyung‐Mi Kee7Tong Yoon Kim8Myungshin Kim9Byung‐Gyu Kim10Jae Sun Ra11Kyungjae Myung12Hongtae Kim13Seung Hun Han14Min‐Duk Seo15Yoonsung Lee16Dong‐Wook Kim17School of Life Sciences Ulsan National Institute of Science and Technology Ulsan Republic of KoreaDepartment of Molecular Science and Technology Ajou University Suwon Republic of KoreaCenter for Genomic Integrity Institute for Basic Science Ulsan Republic of KoreaSchool of Life Sciences Ulsan National Institute of Science and Technology Ulsan Republic of KoreaSchool of Life Sciences Ulsan National Institute of Science and Technology Ulsan Republic of KoreaDepartment of Molecular Science and Technology Ajou University Suwon Republic of KoreaLeukemia Omics Research Institute Eulji University‐Uijeongbu Campus Gyeonggi‐do Republic of KoreaLeukemia Omics Research Institute Eulji University‐Uijeongbu Campus Gyeonggi‐do Republic of KoreaDepartment of Hematology Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul Republic of KoreaDepartment of Laboratory Medicine, College of Medicine The Catholic University of Korea Seoul Republic of KoreaCenter for Genomic Integrity Institute for Basic Science Ulsan Republic of KoreaCenter for Genomic Integrity Institute for Basic Science Ulsan Republic of KoreaSchool of Life Sciences Ulsan National Institute of Science and Technology Ulsan Republic of KoreaSchool of Life Sciences Ulsan National Institute of Science and Technology Ulsan Republic of KoreaDepartment of Medicine Quality Analysis Andong Science College Gyeongbuk Republic of KoreaDepartment of Molecular Science and Technology Ajou University Suwon Republic of KoreaCenter for Genomic Integrity Institute for Basic Science Ulsan Republic of KoreaLeukemia Omics Research Institute Eulji University‐Uijeongbu Campus Gyeonggi‐do Republic of KoreaAbstract Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML). PACSIN2, a novel Cobll1 binding protein, activates TKI‐induced apoptosis in K562 cells, and this activation is suppressed by Cobll1 through the interaction between PACSIN2 and Cobll1. PACSIN2 also binds and inhibits SH3BP1 which activates the downstream Rac1 pathway and induces TKI resistance. PACSIN2 competitively interacts with Cobll1 or SH3BP1 with a higher affinity for Cobll1. Cobll1 preferentially binds to PACSIN2, releasing SH3BP1 to promote the SH3BP1/Rac1 pathway and suppress TKI‐mediated apoptosis and eventually leading to TKI resistance. Similar interactions among Cobll1, PACSIN2, and SH3BP1 control hematopoiesis during vertebrate embryogenesis. Clinical analysis showed that most patients with CML have Cobll1 and SH3BP1 expression at the BC phase and BC patients with Cobll1 and SH3BP1 expression showed severe progression with a higher blast percentage than those without any Cobll1, PACSIN2, or SH3BP1 expression. Our study details the molecular mechanism of the Cobll1/PACSIN2/SH3BP1 pathway in regulating drug resistance and BC progression in CML.https://doi.org/10.1002/cam4.4727blastic transformationchronic myeloid leukemiaCobll1PACSIN2SH3BP1 |
| spellingShingle | Kibeom Park Hee‐Seop Yoo Chang‐Kyu Oh Joo Rak Lee Hee Jin Chung Ha‐Neul Kim Soo‐Hyun Kim Kyung‐Mi Kee Tong Yoon Kim Myungshin Kim Byung‐Gyu Kim Jae Sun Ra Kyungjae Myung Hongtae Kim Seung Hun Han Min‐Duk Seo Yoonsung Lee Dong‐Wook Kim Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia Cancer Medicine blastic transformation chronic myeloid leukemia Cobll1 PACSIN2 SH3BP1 |
| title | Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia |
| title_full | Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia |
| title_fullStr | Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia |
| title_full_unstemmed | Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia |
| title_short | Reciprocal interactions among Cobll1, PACSIN2, and SH3BP1 regulate drug resistance in chronic myeloid leukemia |
| title_sort | reciprocal interactions among cobll1 pacsin2 and sh3bp1 regulate drug resistance in chronic myeloid leukemia |
| topic | blastic transformation chronic myeloid leukemia Cobll1 PACSIN2 SH3BP1 |
| url | https://doi.org/10.1002/cam4.4727 |
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