Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia
<p dir="ltr">Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. β-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2020
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513515993169920 |
|---|---|
| author | Luisa Tomasello (702932) |
| author2 | Marzia Vezzalini (212801) Christian Boni (11729021) Massimiliano Bonifacio (304529) Luigi Scaffidi (12828062) Mohamed Yassin (4166515) Nader Al-Dewik (4166527) Paul Takam Kamga (18561280) Mauro Krampera (292581) Claudio Sorio (212799) |
| author2_role | author author author author author author author author author |
| author_facet | Luisa Tomasello (702932) Marzia Vezzalini (212801) Christian Boni (11729021) Massimiliano Bonifacio (304529) Luigi Scaffidi (12828062) Mohamed Yassin (4166515) Nader Al-Dewik (4166527) Paul Takam Kamga (18561280) Mauro Krampera (292581) Claudio Sorio (212799) |
| author_role | author |
| dc.creator.none.fl_str_mv | Luisa Tomasello (702932) Marzia Vezzalini (212801) Christian Boni (11729021) Massimiliano Bonifacio (304529) Luigi Scaffidi (12828062) Mohamed Yassin (4166515) Nader Al-Dewik (4166527) Paul Takam Kamga (18561280) Mauro Krampera (292581) Claudio Sorio (212799) |
| dc.date.none.fl_str_mv | 2020-03-26T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ijms21072298 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Regulative_Loop_between_-catenin_and_Protein_Tyrosine_Receptor_Type_in_Chronic_Myeloid_Leukemia/25827655 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis β-catenin PTPRG chronic myeloid leukemia methylation tumor suppressor tyrosine phosphatase DNMT 5-azacytidine |
| dc.title.none.fl_str_mv | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. β-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between β-catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene β-Catenin. PTPRG was found to be capable of dephosphorylating β-catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of β-catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and β-catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and β-catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms21072298" target="_blank">https://dx.doi.org/10.3390/ijms21072298</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_40bcb01e45692db9364e10c772d65f59 |
| identifier_str_mv | 10.3390/ijms21072298 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25827655 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid LeukemiaLuisa Tomasello (702932)Marzia Vezzalini (212801)Christian Boni (11729021)Massimiliano Bonifacio (304529)Luigi Scaffidi (12828062)Mohamed Yassin (4166515)Nader Al-Dewik (4166527)Paul Takam Kamga (18561280)Mauro Krampera (292581)Claudio Sorio (212799)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesClinical sciencesOncology and carcinogenesisβ-cateninPTPRGchronic myeloid leukemiamethylationtumor suppressortyrosine phosphataseDNMT5-azacytidine<p dir="ltr">Protein tyrosine phosphatase receptor type γ (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. β-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between β-catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene β-Catenin. PTPRG was found to be capable of dephosphorylating β-catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of β-catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and β-catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and β-catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms21072298" target="_blank">https://dx.doi.org/10.3390/ijms21072298</a></p>2020-03-26T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms21072298https://figshare.com/articles/journal_contribution/Regulative_Loop_between_-catenin_and_Protein_Tyrosine_Receptor_Type_in_Chronic_Myeloid_Leukemia/25827655CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258276552020-03-26T06:00:00Z |
| spellingShingle | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia Luisa Tomasello (702932) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis β-catenin PTPRG chronic myeloid leukemia methylation tumor suppressor tyrosine phosphatase DNMT 5-azacytidine |
| status_str | publishedVersion |
| title | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| title_full | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| title_fullStr | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| title_full_unstemmed | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| title_short | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| title_sort | Regulative Loop between β-catenin and Protein Tyrosine Receptor Type γ in Chronic Myeloid Leukemia |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis β-catenin PTPRG chronic myeloid leukemia methylation tumor suppressor tyrosine phosphatase DNMT 5-azacytidine |