Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in Breast Cancer for Therapeutic Revolution

Cell Biochem Biophys. 2024 Jun;82(2):501-520. doi: 10.1007/s12013-024-01261-5. Epub 2024 Apr 9.

Abstract

The Disabled-2 (DAB2) protein, found in 80-90% of various tumors, including breast cancer, has been identified as a potential tumor suppressor protein. On the contrary, some hypothesis suggests that DAB2 is associated with the modulation of the Ras/MAPK pathway by endocytosing the Grb/Sos1 signaling complex, which produces oncogenes and chemoresistance to anticancer drugs, leading to increased tumor growth and metastasis. DAB2 has multiple functions in several disorders and is typically under-regulated in several cancers, making it a potential target for treatment of cancer therapy. The primary function of DAB2 is the modulation of transforming growth factor- β (TGF-β) mediated endocytosis, which is involved in several mechanisms of cancer development, including tumor suppression through promoting apoptosis and suppressing cell proliferation. In this review, we will discuss in detail the mechanisms through which DAB2 leads to breast cancer and various advancements in employing DAB2 in the treatment of breast cancer. Additionally, we outlined its role in other diseases. We propose that upregulating DAB2 could be a novel approach to the therapeutics of breast cancer.

Keywords: Anti-tumorigenic; Breast cancer; DAB2; Epithelial-mesenchymal transition (EMT); Pro-tumorigenic; Transforming growth factor-β (TGF-β).

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing* / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis Regulatory Proteins* / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Endocytosis
  • Female
  • Humans
  • Signal Transduction* / drug effects
  • Transforming Growth Factor beta / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Adaptor Proteins, Signal Transducing
  • DAB2 protein, human
  • Transforming Growth Factor beta
  • Antineoplastic Agents
  • Tumor Suppressor Proteins