TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment
Pancreatic cancer remains a grueling disease that is projected to become the second-deadliest cancer in the next decade. Standard treatment of pancreatic cancer is chemotherapy, which mainly targets the differentiated population of tumor cells; however, it paradoxically sets the roots of tumor relap...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Cell Press
2021
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| _version_ | 1797101396849328128 |
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| author | Abdel Mouti, M Pauklin, S |
| author_facet | Abdel Mouti, M Pauklin, S |
| author_sort | Abdel Mouti, M |
| collection | OXFORD |
| description | Pancreatic cancer remains a grueling disease that is projected to become the second-deadliest cancer in the next decade. Standard treatment of pancreatic cancer is chemotherapy, which mainly targets the differentiated population of tumor cells; however, it paradoxically sets the roots of tumor relapse by the selective enrichment of intrinsically chemoresistant pancreatic cancer stem cells that are equipped with an indefinite capacity for self-renewal and differentiation, resulting in tumor regeneration and an overall anemic response to chemotherapy. Crosstalk between pancreatic tumor cells and the surrounding stromal microenvironment is also involved in the development of chemoresistance by creating a supportive niche, which enhances the stemness features and tumorigenicity of pancreatic cancer cells. In addition, the desmoplastic nature of the tumor-associated stroma acts as a physical barrier, which limits the intratumoral delivery of chemotherapeutics. In this review, we mainly focus on the transforming growth factor beta 1 (TGFB1)/inhibin subunit beta A (INHBA) homodimer/Nodal-SMAD2/3 signaling network in pancreatic cancer as a pivotal central node that regulates multiple key mechanisms involved in the development of chemoresistance, including enhancement of the stem cell-like properties and tumorigenicity of pancreatic cancer cells, mediating cooperative interactions between pancreatic cancer cells and the surrounding stroma, as well as regulating the deposition of extracellular matrix proteins within the tumor microenvironment. |
| first_indexed | 2024-03-07T05:51:19Z |
| format | Journal article |
| id | oxford-uuid:e8fac427-54d4-46a4-8583-91220b53be42 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:51:19Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:e8fac427-54d4-46a4-8583-91220b53be422022-03-27T10:50:52ZTGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e8fac427-54d4-46a4-8583-91220b53be42EnglishSymplectic ElementsCell Press2021Abdel Mouti, MPauklin, SPancreatic cancer remains a grueling disease that is projected to become the second-deadliest cancer in the next decade. Standard treatment of pancreatic cancer is chemotherapy, which mainly targets the differentiated population of tumor cells; however, it paradoxically sets the roots of tumor relapse by the selective enrichment of intrinsically chemoresistant pancreatic cancer stem cells that are equipped with an indefinite capacity for self-renewal and differentiation, resulting in tumor regeneration and an overall anemic response to chemotherapy. Crosstalk between pancreatic tumor cells and the surrounding stromal microenvironment is also involved in the development of chemoresistance by creating a supportive niche, which enhances the stemness features and tumorigenicity of pancreatic cancer cells. In addition, the desmoplastic nature of the tumor-associated stroma acts as a physical barrier, which limits the intratumoral delivery of chemotherapeutics. In this review, we mainly focus on the transforming growth factor beta 1 (TGFB1)/inhibin subunit beta A (INHBA) homodimer/Nodal-SMAD2/3 signaling network in pancreatic cancer as a pivotal central node that regulates multiple key mechanisms involved in the development of chemoresistance, including enhancement of the stem cell-like properties and tumorigenicity of pancreatic cancer cells, mediating cooperative interactions between pancreatic cancer cells and the surrounding stroma, as well as regulating the deposition of extracellular matrix proteins within the tumor microenvironment. |
| spellingShingle | Abdel Mouti, M Pauklin, S TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title | TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title_full | TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title_fullStr | TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title_full_unstemmed | TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title_short | TGFB1/INHBA homodimer/nodal-SMAD2/3 signaling network: a pivotal molecular target in PDAC treatment |
| title_sort | tgfb1 inhba homodimer nodal smad2 3 signaling network a pivotal molecular target in pdac treatment |
| work_keys_str_mv | AT abdelmoutim tgfb1inhbahomodimernodalsmad23signalingnetworkapivotalmoleculartargetinpdactreatment AT pauklins tgfb1inhbahomodimernodalsmad23signalingnetworkapivotalmoleculartargetinpdactreatment |