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Disable 2, A Versatile Tissue Matrix Multifunctional Scaffold Protein with Multifaceted Signaling: Unveiling Role in
Nidhi N Shah1, Bhavarth P Dave1, Kashvi C Shah1
1Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Navrangpura, Ahmedabad, 380009, Gujarat, India.
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.
Insights
Disabled-2 (DAB2) protein, often found in tumors, may suppress cancer by regulating pathways and promoting apoptosis. Upregulating DAB2 presents a novel therapeutic strategy for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Disabled-2 (DAB2) protein is present in 80-90% of various tumors, including breast cancer.
- DAB2's role is complex, potentially acting as a tumor suppressor or promoting oncogenesis via pathways like Ras/MAPK.
- Under-regulation of DAB2 in cancers suggests its therapeutic potential.
Purpose of the Study:
- To review the mechanisms by which DAB2 contributes to breast cancer development.
- To discuss advancements in utilizing DAB2 for breast cancer treatment.
- To explore DAB2's role in other diseases.
Main Methods:
- Literature review of DAB2's functions in cancer.
- Analysis of DAB2's involvement in signaling pathways (e.g., Ras/MAPK, TGF-β).
- Examination of DAB2's role in endocytosis and apoptosis.
Main Results:
- DAB2 modulates transforming growth factor-β (TGF-β) mediated endocytosis, impacting apoptosis and proliferation.
- DAB2's interaction with the Grb/Sos1 complex influences oncogene production and chemoresistance.
- Evidence suggests DAB2 under-regulation contributes to tumor growth and metastasis.
Conclusions:
- DAB2 plays a multifaceted role in cancer, with potential tumor-suppressive functions.
- Targeting DAB2, particularly through upregulation, offers a promising therapeutic avenue for breast cancer.
- Further research into DAB2's mechanisms could unlock new cancer treatment strategies.
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