The role of zyxin in regulation of malignancies

Abstract

Focal adhesions are highly dynamic multi-protein complexes found at the cell surface and effectively link the cell's internal cytoskeleton to a complex mixture of macromolecules known as the extracellular matrix and mediate transmission of signals from the extracellular matrix to the nucleus. Zyxin is one of the key focal adhesion proteins and is also found to shuttle in the nucleus. Although the mechanism of shuttling to the nucleus unclear, it moves out from the nucleus through a leucine-rich nuclear export signal sequence. It is known to contribute to fundamental cellular activities such as cell migration, adhesion and proliferation by interacting with a variety of cellular proteins. It is also linked with a number of cancers such as melanoma, hepatocellular carcinoma, oral squamous-cell carcinoma, Ewing sarcoma and prostate cancer. However, in many cases, the precise mechanisms by which the absence or presence of zyxin contributes to cancer progression or suppression is unknown. Thus, more work is required to gain insights into how zyxin modulates cellular functions in relationship to cancer. This review summarises the role of zyxin in cancer, with an emphasis on conflicting roles in prostate cancer.

Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival

“…6 ) 42 – 48 . This is in agreement with observations that zyxin influences cell migration, adhesion and proliferation as well as its potential involvement in cancer progression 49 – 53 . Zyxin’s role in regulating cell survival is controversial 27 – 30 , but nuclear activities have generally been related to anti-apoptotic effects 15 , 16 .…”

The Role of Zyxin in Carcinogenesis

“…The research carried out in recent years has confirmed the contribution of ZYX to the development of various cancer types, including melanoma, ovarian, breast, glioma, lung, and oral squamous cell carcinoma (6,(24)(25)(26)(27)(28). Recent observations have revealed that ZYX can act as an oncoprotein or a tumour suppressor, depending on the cancer type (16).…”

“…This hypothesis was proposed when the interaction of ZYX with E6 protein of human papilloma virus 6 (HPV6) was found (65). As it is commonly known, HPV is responsible, inter alia, for the genital warts and leads to cancer development (16,65). It was demonstrated that the interaction of ZYX with a viral molecule causes its translocation into the nucleus.…”

Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells

“…Our results demonstrated a decline in the phosphorylated RB levels upon miR-200c and Par-4 overexpression, which could adequately contribute to their pro-apoptotic effects. Zyxin is a crucial focal adhesion protein, and its involvement is reported in many cancers [ 55 ]. Recently, it has been demonstrated to promote cell migration and invasion [ 38 , 56 ].…”