Loss of protocadherin-17 (PCDH-17) promotes metastasis and invasion through hyperactivation of EGFR/MEK/ERK signaling pathway in hepatocellular carcinoma

Abstract

Metastasis has been one of the major reasons for cancer-related mortality, with multiple genes and pathways being involved in this complex process. Given the molecular variations underlying metastasis of hepatocellular carcinoma (HCC) remains largely unknown; in our previous work, we found copying number of protocadherin-17 (PCDH-17) was significantly deleted in HCC tissues that occurred to metastasize compared with that in the primary HCC without metastasis. Therefore, we hypothesized that PCDH-17 may suppress the metastasis of HCC. There has been, however, no relevant literature available regarding PCDH-17 in HCC. In the present study, we have immunohistochemically detected and clinicopathologically analyzed the expression of PCDH-17 in vivo in clinical tissues; besides, we have explored the role of PCDH-17 ex vivo using a panel of HCC cell lines. It was discovered that PCDH-17 expression was clinically correlated with overall prognosis as well as metastasis in vivo and that PCDH-17 inhibited metastasis via EGFR/MEK/ERK signaling pathway ex vivo. Together, our results obtained both in vivo and ex vivo suggested that activation of EGFR/MEK/ERK signaling pathway through PCDH-17 promotes metastasis in HCC.

Carboxypeptidase E transmits its anti-migratory function in glioma cells via transcriptional regulation of cell architecture and motility regulating factors

“…2C). CD9/MRP-1 is closely linked to plateled derived growth factor mediated glioma cell migration (21), downregulation of MGST1 weakens cell adhesion in PC12 cells (22) whereas PCDh17 regulates actin dynamics and inhibits migration and invasion (23,24). In contrast, many pro-migratory genes like ADAMTS4, MGAT4A, SPP1, STC1 and SNAI2/SLUG are downregulated by sCPE (Fig.…”

PCDHGA12 methylation biomarker in bronchial washing specimens as an adjunctive diagnostic tool to bronchoscopy in lung cancer

“…The regulation of homophilic cell-adhesion proteins, termed protocadherins, is associated with tissue development and growth (7). The epigenetic inactivation of genes that code for protocadherins is associated with the development and growth of several malignant tumor types (8,9). The protocadherin GA12 (PCDHGA12) gene, one of the genes coding for protocadherin, is located on chromosome 5 (10).…”

MiR-196b affects the progression and prognosis of human LSCC through targeting PCDH-17

“…Protocadherin 17 (PCDH-17), also known as PCH68 and PCDH68, belongs to the protocadherin gene family, a subfamily of the cadherin superfamily [19], which is located at human chromosome 13q21.2 [20]. Increasing evidences have revealed the dysregulation of PCDH-17 was involved in multiple tumors, including bladder cancer, colorectal adenocarcinoma, hepatocellular carcinoma and gastric cancer [20][21][22][23]. Notably, Giefing et al found PCDH-17 acted as a tumor suppressor gene in LSCC [24].…”