Abstract
PAQR3 is a newly discovered tumor suppressor and its functional role in breast cancer has not been well characterized. We report here that PAQR3 is associated with the progression and survival of human patients with breast cancer, as well as cell proliferation and migration of human breast cancer cells. PAQR3 mRNA level was robustly downregulated in human breast cancer samples compared with their corresponding para-cancerous histological normal tissues (n = 82, P < 0.0001). The mRNA level of PAQR3 was negatively correlated with HER2 expression (P < 0.0001) and disease-free survival of the patients (P < 0.0001). PAQR3 overexpression inhibited cell proliferation, colony formation and migration of breast cancer cells including MCF7, SKBR3, MDA-MD-231, MDA-MD-468 and MDA-MD-453 cells. Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration. Inhibition of HER2 by trastuzumab increased PAQR3 expression in SKBR3 cells. In conclusion, PAQR3 expression is frequently downregulated in human breast cancers inversely correlated with HER2 expression. PAQR3 is able to modulate the proliferation and migration of breast cancer cells. Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.
Highlights
Breast cancer is one of the most common cancers worldwide
Consistent with the clinical data that human epidermal growth factor receptor 2 (HER2) expression is inversely correlated with PAQR3 expression, we found that the HER2-negative MDA-MD-231 cells had the highest level of PAQR3 expression (Figure 3A)
Since our clinical data indicate that PAQR3 expression level is inversely correlated with HER2 expression level, we explored the regulation of HER2 by PAQR3 and vice versa
Summary
Breast cancer is one of the most common cancers worldwide. Risk factors for developing breast cancer include obesity, lack of physical exercise, drinking alcohol, hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, and having children late or not at all. Breast cancer cells bear (noun-verb agreement) different receptors on their surface and in their cytoplasm or nucleus, among these receptors the important ones are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [2]. These receptors especially HER2 have served as targets for treatment of breast cancers [3]. PAQR3 functions as a tumor suppressor mainly due to its inhibitory activity on Raf/MAPK and PI3K/Akt signaling pathways [15,16,17,18,19]. We investigated the potential functions of PAQR3 in human breast cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
