CLDN6 inhibits colorectal cancer proliferation dependent on restraining p53 ubiquitination via ZO-1/PTEN axis
Copyright © 2023. Published by Elsevier Inc..
Colorectal cancer (CRC) is one of the most common cancers in the world. Abnormal proliferation is a chief characteristic of cancer and is the initiation of CRC progression. As an important component of tight junctions, CLDN6 regulates the proliferation of multiple tumors. Our previous study showed that CLDN6 was low expressed in CRC, and CLDN6 overexpression inhibited CRC proliferation. However, the specific mechanism of how CLDN6 works remains unclear. This research aimed to reveal the relationship between CLDN6 and clinical features, as well as the molecular mechanism by which CLDN6 inhibited CRC proliferation. We found that low expression of CLDN6 was associated with pathological grade and prognosis of CRC patients, and confirmed that CLDN6 inhibited CRC proliferation dependent on p53. Mechanically, we elucidated that CLDN6 regulated ubiquitination to enhance p53 stability and nuclear import by PTEN/AKT/MDM2 pathway. Through the PDZ-binding motif (PBM), CLDN6 bound to ZO-1 to interact with PTEN, and regulate AKT/MDM2 pathway. Collectively, our data enriched the theoretical basis for CLDN6 as a potential biomarker for diagnosis, therapy and prognosis of CRC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:112 |
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| Enthalten in: |
Cellular signalling - 112(2023) vom: 01. Dez., Seite 110930 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dong, Yuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.11.2023 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cellsig.2023.110930 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a Colorectal cancer (CRC) is one of the most common cancers in the world. Abnormal proliferation is a chief characteristic of cancer and is the initiation of CRC progression. As an important component of tight junctions, CLDN6 regulates the proliferation of multiple tumors. Our previous study showed that CLDN6 was low expressed in CRC, and CLDN6 overexpression inhibited CRC proliferation. However, the specific mechanism of how CLDN6 works remains unclear. This research aimed to reveal the relationship between CLDN6 and clinical features, as well as the molecular mechanism by which CLDN6 inhibited CRC proliferation. We found that low expression of CLDN6 was associated with pathological grade and prognosis of CRC patients, and confirmed that CLDN6 inhibited CRC proliferation dependent on p53. Mechanically, we elucidated that CLDN6 regulated ubiquitination to enhance p53 stability and nuclear import by PTEN/AKT/MDM2 pathway. Through the PDZ-binding motif (PBM), CLDN6 bound to ZO-1 to interact with PTEN, and regulate AKT/MDM2 pathway. Collectively, our data enriched the theoretical basis for CLDN6 as a potential biomarker for diagnosis, therapy and prognosis of CRC | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CLDN6 | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Proliferation | |
| 650 | 4 | |a Ubiquitination | |
| 650 | 4 | |a p53 | |
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| 700 | 1 | |a Qi, Da |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Huinan |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Qiu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Minghao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Quan, Chengshi |e verfasserin |4 aut | |
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