The Impact of Protein Tyrosine Phosphatase [SHP2] Inhibitors on the Progression of Head and Neck Squamous Cell Carcinoma

Author(s)

Dhruvi PatelFollow

School Name

South Carolina Governor's School for Science & Mathematics

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Abstract

Head and Neck Squamous Cell Carcinoma is a disease that originates from the squamous cells lining the mucosal surfaces of the head and neck, with about 450,000 cases found annually. Involvement of tyrosine phosphorylation in the development of this cancer has previously been known to be caused by mutations of kinases. However, in recent studies, it has been found that these cancers can also be caused by mutations of phosphatases. The aim of this research is to test the impact of Protein Tyrosine Phosphatases such as Src Homology Phosphatase 2 (SHP2) on various oral SCC cell lines [UM-SCC12, UM-SCC4, UM-SCC21, and HGF-1] as well as the impact of various inhibitors on the activity of SHP2. This was achieved using the Western blot analysis to determine protein levels, MTT assay used to determine cell proliferation, and Motility assay used to determine cell migration; these results were compared to those of untreated cells. The preliminary results of the Western Blot analysis showed that SHP2 phosphatase activity is required for ERK (signaling pathway) activation and maintenance of cell growth in RTK-driven cancers. The MTT assay indicated that compared to other non-specific phosphatase inhibitors, the specific inhibitor SHP099 is well tolerated as evidenced by highest percentage of viable cells among the tested concentrations. The Motility assay indicated that inhibition of SHP2 causes a decrease in cell movement. Therefore, it is possible for the specific inhibitor (SHP099) to be used as a therapeutic drug to slow the progression of cancer.

Location

Furman Hall 107

Start Date

3-28-2020 1:45 PM

Presentation Format

Oral Only

Group Project

No

COinS
 
Mar 28th, 1:45 PM

The Impact of Protein Tyrosine Phosphatase [SHP2] Inhibitors on the Progression of Head and Neck Squamous Cell Carcinoma

Furman Hall 107

Head and Neck Squamous Cell Carcinoma is a disease that originates from the squamous cells lining the mucosal surfaces of the head and neck, with about 450,000 cases found annually. Involvement of tyrosine phosphorylation in the development of this cancer has previously been known to be caused by mutations of kinases. However, in recent studies, it has been found that these cancers can also be caused by mutations of phosphatases. The aim of this research is to test the impact of Protein Tyrosine Phosphatases such as Src Homology Phosphatase 2 (SHP2) on various oral SCC cell lines [UM-SCC12, UM-SCC4, UM-SCC21, and HGF-1] as well as the impact of various inhibitors on the activity of SHP2. This was achieved using the Western blot analysis to determine protein levels, MTT assay used to determine cell proliferation, and Motility assay used to determine cell migration; these results were compared to those of untreated cells. The preliminary results of the Western Blot analysis showed that SHP2 phosphatase activity is required for ERK (signaling pathway) activation and maintenance of cell growth in RTK-driven cancers. The MTT assay indicated that compared to other non-specific phosphatase inhibitors, the specific inhibitor SHP099 is well tolerated as evidenced by highest percentage of viable cells among the tested concentrations. The Motility assay indicated that inhibition of SHP2 causes a decrease in cell movement. Therefore, it is possible for the specific inhibitor (SHP099) to be used as a therapeutic drug to slow the progression of cancer.