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Are Wnt/β-Catenin and PI3K/AKT/mTORC1 Distinct Pathways in Colorectal Cancer?
Open accessAbstract
Wnt/β-catenin and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathways both are critically involved in colorectal cancer (CRC) development, although they are implicated in the modulation of distinct oncogenic mechanisms. In homeostatic and pathologic conditions, these pathways show a fine regulation based mainly on feedback mechanisms, and are connected at multiple levels involving both upstream and downstream common effectors. The ability of the Wnt/β-catenin and PI3K/AKT/mTORC1 pathways to reciprocally control themselves represents one of the main resistance mechanisms to selective inhibitors in CRC, leading to the hypothesis that in specific settings, particularly in cancer driven by genetic alterations in Wnt/β-catenin signaling, the relationship between Wnt/β-catenin and PI3K/AKT/mTORC1 pathways could be so close that they should be considered as a unique therapeutic target. This review provides an update on the Wnt/β-catenin and PI3K/AKT/mTORC1 pathway interconnections in CRC, describing the main molecular players and the potential implications of combined inhibitors as an approach for CRC chemoprevention and treatment.
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“the ability of the Wnt/β‐catenin and PI3K/AKT/mTORC1 pathways to compensate for one another is one of the main mechanisms of chemoresistance [51]”
From Pyrvinium Pamoate Alone and With Gemcitabine Exhibits Anti‐Pancreatic Cancer Activity in 2D and 3D Cell Culture Models (2024) · cites this paper as [51]
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Metadata
- Authors
- Prossomariti, A., Piazzi, G., Alquati, C., & Ricciardiello, L.
- Affiliations
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Corresponding author
- Prossomariti, Anna
- Ricciardiello, Luigi
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2020
- Volume
- 10
- Issue
- 3
- Pages
- 491-506
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC7369353
- OpenAlex
- W3017979273
- Cited by
- 155
- References
- 167
- Citations by year
- 2026: 20 · 2025: 30 · 2024: 36 · 2023: 25 · 2022: 19 · 2021: 20 · 2020: 5
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- Wnt/β-catenin signaling, PI3K/Akt/mTORC1 pathway, colorectal cancer, pathway crosstalk, intestinal tumorigenesis, drug resistance, chemoprevention, feedback regulation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Phosphoinositide-3 Kinase Inhibitors, Animals, Antineoplastic Combined Chemotherapy Protocols, Disease Models, Animal, Humans, Colorectal Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt, Wnt Proteins, beta Catenin
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