The Role of C1q Tumor Necrosis Factor-related Protein 6 in Breast Cancer

Overview

Globally, breast cancer is one of the most prevalent cancers in women and is the second leading cause of cancer death , representing 15% of worldwide deaths per year . In Egypt, it accounts for 32 % of cancer in women with a high mortality rate.

Globally, breast cancer is one of the most prevalent cancers in women and is the second leading cause of cancer death , representing 15% of worldwide deaths per year. In Egypt, it accounts for 32 % of cancer in women with a high mortality rate. The etiology of breast cancer is multifactorial in which multiple epigenetic and genetic variations affect its incidence and prognosis . Although diagnostic methods and therapeutic strategies for breast cancer have been improved in past decades, long-term survival of breast cancer patients still remains poor due to high proliferation, metastasis and post-surgical recurrence rate. Therefore, it is critical to develop more effective screening methods that can detect BC at an early stage and novel therapeutic targets for better treatment. This may be achieved by understanding the molecular mechanisms underlying the initiation and progression of this malignancy. Complement C1q tumor necrosis factor-related protein (CTRPs) are a protein family of adiponectin paralogs which contains fifteen members, CTRP1- CTRP15. This super family are involved in several biological processes, including metabolism, immunity, inflammation, apoptosis and cell differentiation (15, 16). Accumulating evidence correlates CTRP family members with carcinogenesis and signaling pathways associated with cancer development, progression and metastasis. C1q tumor necrosis factor-related protein 6 (CTRP6) or (C1qTNF6) is a member of CTRPs family. It contains four domains including signal peptide, short N-terminal variable region, collagen domain and C-terminal C1q domain. It is expressed mainly in placenta, heart, uterus and adipose tissue. CTRP6 is involved in multiple physiological processes, such as regulating cell proliferation and differentiation. It also mediates fatty acid oxidation, adipogenesis and insulin sensitivity, attenuates cell fibrosis and displays anti-inflammatory properties. Although recent studies have revealed that adiponectin has an inhibitory role in carcinogenesis, the role of CTRP6 in carcinogenesis remains unclear. CTRP6 was initially found to be overexpressed and possibly contributes to tumor angiogenesis in many hepatocellular carcinomas. Moreover, recent research indicates that CTRP6 is correlated with gastric cancer progression by mediating proliferation, migration and apoptosis, which reveals a similar pattern in lung adenocarcinoma. However, tumor suppressor functions of CTRP6 were also successively reported. CTRP6 was found to have inhibitory effect on the proliferation and migration of ovarian cancer cells. Moreover, CTRP6 significantly suppressed the growth and invasion activity of the oral squamous cell carcinoma cells. The role CTRP6 plays in breast cancer is yet unknown. The present study will investigate the level of CTRP6 in BC specimens. Furthermore, the pathological functions of CTRP6 in BC, including cell growth, proliferation, migration, and effect on inflammation and angiogenesis will be studied in breast cancer cells.

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