Title

Grp94: A Possible Therapeutic Target for Multiple Myeloma

School Name

Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Abstract

Multiple Myeloma is a malignant plasma-cell cancer with little known about its pathogenesis and no cure. Previous studies attribute the cancer’s development to the upregulation of the Unfolded Protein Response (UPR) of its cells. This is an evolutionally conserved process that responds to an abundance of misfolded or unfolded proteins released from the endoplasmic reticulum. Among the signaling cascades of the UPR, grp94 is a downstream chaperone protein that assists in the folding of proteins. This protein chaperone proves to be a promising target because greater concentration of the glycoprotein shows a correlation with worsening stages of Multiple Myeloma. If the inhibition of grp94 has a negative impact on the cancer’s cell survival, then this supports its use as a promising therapeutic target. Western Blots and Cell Proliferations Assays were conducted to measure the effects of WS13 (a grp94 inhibitor) on Multiple Myeloma plasma cell survival. From the results, WS13 decreases cell proliferation. The Western Blots of Caspase-7 and HSP90 reveal that grp94 induces apoptosis of the Multiple Myeloma cells, but does not induce UPR. Since grp94 is linked to the pathogenesis of the malignant cancer and the UPR, then the fact this study supports that the inhibitor does not induce UPR, but decreases cell proliferation is promising. From this study, the inhibition of grp94 is a promising method for decreasing cell survival of Multiple Myeloma cells.

Location

Neville 106

Start Date

4-14-2018 9:45 AM

Presentation Format

Oral and Written

COinS
 
Apr 14th, 9:45 AM

Grp94: A Possible Therapeutic Target for Multiple Myeloma

Neville 106

Multiple Myeloma is a malignant plasma-cell cancer with little known about its pathogenesis and no cure. Previous studies attribute the cancer’s development to the upregulation of the Unfolded Protein Response (UPR) of its cells. This is an evolutionally conserved process that responds to an abundance of misfolded or unfolded proteins released from the endoplasmic reticulum. Among the signaling cascades of the UPR, grp94 is a downstream chaperone protein that assists in the folding of proteins. This protein chaperone proves to be a promising target because greater concentration of the glycoprotein shows a correlation with worsening stages of Multiple Myeloma. If the inhibition of grp94 has a negative impact on the cancer’s cell survival, then this supports its use as a promising therapeutic target. Western Blots and Cell Proliferations Assays were conducted to measure the effects of WS13 (a grp94 inhibitor) on Multiple Myeloma plasma cell survival. From the results, WS13 decreases cell proliferation. The Western Blots of Caspase-7 and HSP90 reveal that grp94 induces apoptosis of the Multiple Myeloma cells, but does not induce UPR. Since grp94 is linked to the pathogenesis of the malignant cancer and the UPR, then the fact this study supports that the inhibitor does not induce UPR, but decreases cell proliferation is promising. From this study, the inhibition of grp94 is a promising method for decreasing cell survival of Multiple Myeloma cells.