Periostin in development and progression of colorectal cancer

Faculty Development Competitive Research Grant Program 2019-2021

Cancer is one of the leading causes of mortality worldwide. An estimated 14 Million new cases of cancer occur worldwide every year with the numbers rising over the last decades. Colorectal cancer is one of the most common malignancies world-wide with around 1.2 million new cases being diagnosed each year. The first line of treatment is surgery with additional chemotherapy. In about half of the cases prognosis is poor with 40 % of patients dying in the first 5 years after diagnosis. Metastasis are found in about 20% of the patients being diagnosed with colorectal cancer and will develop in about 50% of patients in the course of their disease. It is therefore essential to develop new treatments as well as means for earlier diagnosis to increase the chances of survival for people afflicted with this disease. The matricellular protein periostin has been shown to be involved in colorectal as well as other cancer.

Periostin is a matricellular protein originally isolated from osteoblasts and found to be preferentially expressed in the periosteum. Periostin contains an N-terminal secretory signal peptide, followed by a cysteine-rich domain, four internal homologous repeats, and a C-terminal hydrophilic domain. The four internal repeats exhibit homology to the axon guidance protein fasciclin I that is involved in the development of nervous system in invertebrates and were thus named fasciclin domains. Periostin has been shown to be upregulated in a variety of different tumors among them colorectal cancer. It has shown that high expression of periostin is linked to poor prognosis. Periostin has been shown to have a variety of different functions in tumor progression including epithelial-mesenchymal transition, niche formation, tumor survival and angiogenesis.
There exist different splice variants of periostin leading to different protein isoforms of periostin. The different isoforms are produced by alternative splicing of the 3’ exons 17 to 22. Each of these exons has a length consisting of multiples of 3 nucleotide. Therefore deletion of any of the exons does not induce a frame shift. The resulting isoforms thus differ only by short stretches of amino acid sequences. It is thought that these differences are responsible for the different functions of periostin.
In this project we plan to analyse the role of periostin in the development and progression of colon cancer. We will be looking at the expression pattern and –profile of periostin at different stages and types of colorectal cancer. This will help elucidate the role of the different isoforms of periostin in tumor development and progression.