Calmegin (CLGN) is a testis-specific endoplasmic reticulum (ER) Ca2+-binding chaperone protein essential for the correct folding of sperm proteins (eg. ADAM1/ADAM2) required for normal sperm maturation and function. CLGN is part of the Cancer Testis Antigens (CTAs) group and is involved in the promotion of tumour growth. CLGN expression was significantly upregulated in many prevalent cancer types including breast cancer, which indicates a potential role for CLGN as a biomarker of cancer or a therapeutic target. Additional studies are warranted to investigate the role of CLGN in breast cancers.
We hypothesize that CLGN may function as oncogene in human breast cancers.
Aims and Objectives:
The main aim of this project is functional characterization of CLGN in subtypes of breast cancer. Preliminary data from the Gupta Group shows that CLGN expression was significantly elevated in primary breast cancer as compared to normal tissue. CLGN was expression significantly upregulated during conditions of UPR in breast cancer cells.
The objectives of the project are:
Objective 1: Generate a panel of breast cancer cell lines [ER-positive (MCF7, T47D) and HER2-enriched (SKBR3) and TNBC (MDA-MB231) cells] with gain-of-function and loss-of-function of CLGN.
Objective 2: Determine the effects of CLGN on cell growth, migration and invasion of ER-positive (MCF7, T47D) and HER2-enriched (SKBR3) and TNBC (MDA-MB231) cells.
The results will present opportunities to modulate CLGN expression to limit tumour growth and improve responsiveness to standard therapies for breast cancer. Additionally, on the occasion that CLGN demonstrate oncogenic properties it could act as a potential biomarker for breast cancer.