Wnt pathway

Posts sharing a common thread:
Post #1: "Kidney Cancer Caused by "Sleeping Gene"? Rise and Shine!!!!"

Primary research:
Gumz, M.L. et al. (2007) Secreted Frizzled-Related Protein 1 Loss Contributes to Tumor Phenotype of Clear Cell Renal Cell Carcinoma. Clinical Cancer Research; 13(16)

Post #2: "GPRC5A Can be the Key to Lung Cancer"

Primary research:
"Tao, Q., Fujimoto, J., Men, T., Ye, X., Deng, J., Lacroix, L. & et al. (2007, November 13 ). Identification of the Retinoic Acid – Inducible Gprc5a As a New Lung Tumor Suppressor Gene. Journal of the National Cancer Institute, 99(22), 1668-1682."

The “Sleeping Gene” post and the “GPRC5A Can be the Key to Lung Cancer” post discuss tumor suppressor genes that affect the Wnt signaling pathway, which controls cell proliferation. The articles mention that either sFRP1 or GPRC5A suppress or inhibit proliferation in cancer by affecting the Wnt signaling pathway. Both sFRP1 and GPRC5A are identified as tumor suppressor genes because they both suppress cell proliferation and cell survival. The normal Wnt signaling system involves the following pathways.

When Wnt is present:

1. GSK3 is inhibited and cannot destroy beta-catenin

2. beta-catenin can enter nucleus and activate other proteins

3. expression of cell proliferation genes turned on

When Wnt is absent:

1. GSK3 binds with beta-catenin

2. beta-catenin is target for degradation
   

Post #2: "GPRC5A Can be the Key to Lung Cancer"

Primary research:
"Tao, Q., Fujimoto, J., Men, T., Ye, X., Deng, J., Lacroix, L. & et al. (2007, November 13 ). Identification of the Retinoic Acid – Inducible Gprc5a As a New Lung Tumor Suppressor Gene. Journal of the National Cancer Institute, 99(22), 1668-1682."

The blog entitled "GPRC5A Can Be the Key to Lung Cancer" mentions GPRC5A is a protein-coupled receptor that is deleted in the lung cancer. SFRP1 means Secreted Frizzled-Related Protein 1. In kidney cancer cells, SFRP1 is missing when tumors are present. The blog post "Sleeping Gene" says that sFRP1 (Secreted Frizzled-Related Protein 1) functions in the Wnt signaling pathway to prevent tumor growth and metastisis. immediately referred to “GPRC5A Can be the Key to Lung Cancer” that GPRC5A may inhibit, the Wnt pathway by acting in the noncanoical Wnt pathway which caught my attention. The noncanonical Wnt pathway is connected to the Wnt pathway, but it functions against the Wnt signaling. When Wnt is around, cells usually proliferate. These noncanonical pathways try to stop Wnt signaling. They suppress, or inhibit, normal canonical Wnt signaling. Both articles mention sFRP1 and GPRC5A normally may (they don't know for sure about GPRC5A) suppress or inhibit proliferation by their effects on the Wnt signaling pathway. Both sFRP1 and GPRC5A are identified as tumor suppressor genes and both are deleted in the tumor cells. The primary source “Identification of the Retinoic Acid – Inducible Gprc5a As a New Lung Tumor Suppressor Gene” stated in the discussion that GPRC5A receptor binds to the seven - transmembrane frizzled receptor that may activate the noncanonical Wnt signaling. Another thing that triggers my interest is sFRP1 could be the frizzled receptor that is mentioned in the second article, “Secreted Frizzled-Related Protein 1 Loss Contributes to Tumor Phenotype of Clear Cell Renal Cell Carcinoma”.

The blog post, "Sleeping Gene." mentions that many renal cell carcinomas are resistant to chemotherapy and radiation treatments. "GPRC5A" mentionsthat the researchers still do not know what is the ligand for GPRC5A receptor and still wondered whether or not it functions in the noncanonical Wnt system. The blog entitled "Sleeping Gene" mentions sFRP1 stops signaling from causing uncontrollable proliferation and metastasis through the Wnt pathway.Since beta-catenin in the Wnt pathway is the key to proliferation, can researchers make a drug targeting beta-catenin to cure the cancers? Would researchers link these two tumor suppressor genes together further studies?