Wnt/β-catenin signaling pathway: an attractive potential therapeutic target in osteosarcoma

Yi Ding1,2, Qin Chen1,2

  • 1Department of Spine Surgery, Ganzhou People's Hospital, Ganzhou, China.

Frontiers in Oncology
|March 3, 2025
PubMed

Insights

Targeting the Wnt/β-catenin pathway shows promise for treating osteosarcoma (OS). Inhibiting this pathway can reverse pathological processes, offering new therapeutic strategies for this common childhood bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Osteosarcoma (OS) is a prevalent bone cancer in children and adolescents with poor long-term survival rates.
  • Current neoadjuvant chemotherapy for OS has limitations, necessitating novel treatment approaches.
  • Aberrant signaling pathways, particularly Wnt/β-catenin, are implicated in cancer development and progression.

Purpose of the Study:

  • To review the role and mechanisms of the Wnt/β-catenin signaling pathway in osteosarcoma.
  • To explore the therapeutic potential of targeting the Wnt/β-catenin pathway for OS treatment.
  • To identify current research gaps and future directions for Wnt/β-catenin pathway-targeted therapies in OS.

Main Methods:

  • Literature review of studies on Wnt/β-catenin signaling in osteosarcoma.
  • Analysis of the molecular mechanisms underlying Wnt/β-catenin pathway involvement in OS.
  • Discussion of therapeutic strategies targeting the Wnt/β-catenin pathway.

Main Results:

  • The Wnt/β-catenin pathway is a key driver in osteosarcoma development and progression.
  • Abnormal Wnt/β-catenin activation promotes OS cell proliferation, invasion, migration, angiogenesis, and chemoresistance.
  • Inhibition of the Wnt/β-catenin pathway demonstrates potential to reverse these pathological processes.

Conclusions:

  • The Wnt/β-catenin pathway is a significant therapeutic target for osteosarcoma.
  • Targeting this pathway offers a promising strategy to improve treatment efficacy and patient outcomes in OS.
  • Further research is needed to overcome current limitations and optimize Wnt/β-catenin-targeted therapies for OS.

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.6K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K