SCRIB protein seems to be a tumor suppressor of liver cancer

Researchers have discovered a tumor suppressor in human liver cancer. Although it is not easy to selectively target the tumor suppressor, the study extends our understanding of liver cancer pathogenesis.

SCRIB is a scaffold protein that in humans is encoded by the SCRIB gene. This protein is found as a membrane protein and it regulates the establishment of apical-basal cell polarity of the epithelial tissues. Previous studies have shown that SCRIB also plays a role in cancer progression. For example, SCRIB is mislocalized to the cytoplasm in breast and prostate cancer.

The new study indicates that the SCRIB protein not only translocates to the cytoplasm but also to the nucleus in liver cancer. Led by Augusta University and National Cancer Institute, the study reveals that up-regulation of SCRIB inhibits the growth of hepatocellular carcinoma (HCC) cells in vitro, and down-regulation of SCRIB promotes the growth of liver tumors in vivo.

The study, “The cell polarity protein Scrib functions as a tumor suppressor in liver cancer,” appears in Oncotarget. Ande Satyanarayana is the corresponding author.

HCC is a highly aggressive vascular cancer and is the most common type of liver cancer, which involves diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. There are about 500,000 to 1,000,000 new cases of HCC per year. And its incidence is on the rise in many countries. Currently, the five-year survival rate is only 1–4%. More effective therapies are in urgent need.

SCRIB is an evolutionarily conserved component of a common genetic pathway which is involved in apical-basal cell polarity. The protein appears to regulate multiple cellular processes, such as cell proliferation, differentiation, apoptosis, and migration, by interacting with other proteins.

SCRIB has been identified as a tumor suppressor gene in the fruit fly Drosophila. Mutations in the gene lead to disruption of cell polarity and neoplastic overgrowth of tissues. However, there are conflicting reports regarding the role of SCRIB in human cancers. Some reports indicate that down-regulation and cytoplasmic localization of Scrib are commonly present in several human cancers, including colon, ocular, endometrial and breast cancers; while others suggest that the protein is over-expressed in most human cancers. These data shows that the protein SCRIB may not only function as a tumor suppressor but also as an oncogene, and its function is related to the type of cancer.

For the current study, the team looked at the function of SCRIB in HCC. They found that some SCRIB moves to the cytoplasm and nucleus, and it works to inhibit expression of the oncogenes Yap1, c-Myc and cyclin D. They also observed increased SCRIB expression in 70% of human liver tumors analyzed. Taken together, the results demonstrate that the protein SCRIB acts as a tumor suppressor in human liver cancer. The researchers concluded that “the expression, localization and whether Scrib functions as a tumor suppressor or oncogene appears to be rather complex and depends on the cancer type.” (Cusabio offers SCRIB, Yap1, c-Myc and cyclin D related proteins and antibodies and other products like Recombinant SRD5A2 for research.)