ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: FR-PO1033

Targeting MTAP-Deficient Cells in Advanced Renal Cell Carcinoma

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Xu, Jihao, UC Davis, Davis, California, United States
  • Yang, David, UC Davis, Davis, California, United States
  • Weiss, Robert, UC Davis, Davis, California, United States
  • Chen, Ching-Hsien, UC Davis, Davis, California, United States

The metabolic enzyme methylthioadenosine phosphorylase (MTAP) has been reported to function as a tumor suppressor and the lack of this gene was found in approximately 58% of kidney cancer (or renal cell carcinoma, RCC) cases. However, the mechanisms of how MTAP regulates RCC progression still remain unknown.


Tissue microarray and immunohistochemistry (IHC) were performed to analyze the correlation between MTAP expression and IGF-1R phosphorylation in RCC. A phospho-receptor tyrosine kinase array screen was utilized to assess RCC signaling pathway activity. Genetic manipulations were achieved by siRNA knockdown, CRISPR/Cas9 and ectopic expression approaches. In addition, we used an IGF-1R inhibitor, linsitinib, to suppress type 1 Insulin Growth Factor 1 Receptor (IGF-1R) signaling. In vitro and in vivo tumor suppressive activities of MTAP were confirmed by MTT, colony formation, migration assays and in vivo subcutaneous implantation. MTAP-regulated gene expression and signaling were determined by qRT-PCR and Western blots.


We found a decrease of protein-methylation level concomitant with an increase in tyrosine phosphorylation in MTAP-knockout cells. We next performed a receptor tyrosine kinase array screen and identified IGF1R as the top-one candidate with upregulated tyrosine phosphorylation in response to MTAP loss. Western blots showed an elevation of IGF1R phosphorylation and its signaling after MTAP knockout. IHC staining on a tissue microarray has also confirmed an inversely association between IGF-1R phosphorylation and MTAP expression. We noticed a decrease of cell viability, migration, invasion and colony-forming capabilities in MTAP-knockout RCC cells after linsitinib treatment. Surprisingly, RCC cells were more sensitive to this inhibitor in response to MTAP loss, suggesting that MTAP-deficient become addicted to IGF1R activity.


IGF-1R signaling is a driver pathway conferring aggressive nature to MTAP-deleted renal cell carcinomas.


  • Commercial Support