The role of SIPA1 in the development of cancer and metastases (Review)

Abstract

Cancer is a leading cause of mortality and the majority of deaths are due to metastases. Many molecules have been implicated in the development of metastases. Signal induced proliferation associated protein 1 (SIPA1), a mitogen-inducible gene, has been demonstrated to be involved in the metastasis of various solid tumours and may indicate a poor prognosis. Polymorphisms of SIPA1 can be associated with several different types of cancer and interactions between SIPA1 and binding molecules integrate a series of cellular functions, which may promote the development and metastasis of cancer. The mechanisms by which SIPA1 promotes the development and metastasis of cancer varies among tumour types. The present review describes the structure, function and regulation of SIPA1 and focuses on its role in cancer metastasis. Possibilities for future research and the clinical application of SIPA1 are also discussed.

Keywords: cancer; metastasis; signal induced proliferation associated protein 1; tight Junctions.

Figure 1

Structure of the human SIPA1 gene and protein. (A) Schematic representation of the SIPA1 gene structure. (B) The 16 exons of the SIPA1 gene. (C) Schematic representation of the SIPA1 protein structure. SIPA1, signal induced proliferation associated protein 1.

Figure 2

Schematic diagram presenting the interacting molecules of SIPA1. SIPA1 is central to the presented interactions. SIPA1 regulates the transcription of ITGB1 and controls proteins of the MMP family. Rap1 inhibition may modulate MMP via Akt signalling. AF6, presented in red, is the key molecule by which SIPA1 directly affects and adjusts tight junction proteins, maintaining cell-to cell barrier function. SIPA1, signal induced proliferation associated protein 1; ITGB1, integrin β1 promoter; MMP, matrix metallopeptidase; AF6, afadin.