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

• Published in: Cell biochemistry and biophysics Vol. 82; no. 2; pp. 501 - 520
• Main Authors: Shah, Nidhi N., Dave, Bhavarth P., Shah, Kashvi C., Shah, Disha D., Maheshwari, Kunal G., Chorawala, Mehul R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2024; Springer Nature B.V
• Subjects: Antineoplastic drugs; Apoptosis; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Breast cancer; Cancer therapies; Cell Biology; Cell proliferation; Chemoresistance; Chemotherapy; Disabled-2 protein; Endocytosis; Growth factors; Life Sciences; MAP kinase; Metastases; Modulation; Pharmacology/Toxicology; Proteins; Review Paper; Transforming growth factor-b; Tumor suppression; Tumor suppressor genes; Tumors; Anti-tumorigenic; DAB2; Epithelial-mesenchymal transition (EMT); Breast cancer; Pro-tumorigenic; Transforming growth factor-β (TGF-β)
• ISSN: 1085-9195; 1559-0283; 1559-0283
• DOI: 10.1007/s12013-024-01261-5

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.