Cellular Protein Degradation Pathways

Study focusing on human Sodium-dependent Multi Vitamin Transporter (hSMVT) and its application in cancer cell targeting

By: Arjun G.
Year: 2023
School: Los Alamitos High
Grade: 11
Science Teacher: Brighton Merrell

In the realm of scientific exploration, few projects carry the promise of transforming lives as much as Arjun’s groundbreaking study on the human Sodium-dependent Multivitamin Transporter (hSMVT) and its potential application in targeting cancer cells. With colon cancer standing as the third leading cause of cancer-related deaths globally, Arjun’s research takes us one step closer to a more effective and targeted approach to combating this deadly disease.

Understanding the Role of hSMVT

Colon cancer has left an indelible mark on public health, accounting for over 940,000 deaths worldwide in the year 2020 alone. One significant avenue of research lies in the overexpression of specific membrane-bound proteins, such as the Sodium-dependent Multivitamin Transporter (SMVT), which have been identified as key players in the targeting of colonic cancer cells.

Arjun’s pioneering project delves deep into the study of hSMVT, focusing on its regulation, functionality, and potential in cancer therapy. The primary objective revolves around investigating whether SMVT’s overexpression in cancer cells can be harnessed for precise drug delivery, thus paving the way for more effective treatment strategies.

Probing SMVT Regulation and Functionality

A critical aspect of Arjun’s research involves the analysis of SMVT regulation within cancer cells. Employing innovative techniques, Arjun explored the proteasomal and lysosomal degradation pathways using inhibitors like Lactacystin and Bafilomycin. Remarkably, the results of these experiments revealed a notable increase in SMVT expression following inhibitor treatment, pointing toward a potential ubiquitin-mediated degradation pathway.

To assess SMVT’s functionality, Arjun conducted experiments to investigate its role in biotin uptake within cancer cells. The outcomes were significant – both proteasomal and lysosomal pathway inhibitors led to an augmented biotin uptake, indicating that the overexpressed SMVT proteins remain fully functional. This discovery is pivotal, suggesting that SMVT can indeed be leveraged for targeted drug delivery.

The Biotin Conjugate Breakthrough

One of the most exciting facets of Arjun’s project lies in the creation of a biotin cancer drug conjugate, specifically utilizing the drug temozolomide. By capitalizing on the understanding of SMVT’s functional role and its potential for drug delivery, Arjun designed a model for the biotin conjugate using the protein model Mhp1, a close homolog of SMVT. The docking experiments yielded astonishing results, identifying five potential binding sites for the biotinylated conjugate, with the strongest interaction boasting a binding energy of -8.9 kCal/mole.

Arjun’s research provides a profound insight into SMVT protein expression within the context of cancer therapy. The findings substantiate the hypothesis of functional SMVT proteins in cancer cells, thus dispelling the notion that protein overexpression is a result of evasion from ubiquitination. Instead, the overexpression of the SMVT gene emerges as a prime driver of heightened protein expression within cancer cells.

The study’s implications reach beyond colon cancer, paving the way for a framework of drug targeting in various other forms of cancer that also exhibit SMVT overexpression. This holds immense promise for the future of cancer therapy, offering a novel and precise approach that can potentially revolutionize treatment strategies and improve patient outcomes.