1. School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, Shaanxi, China.
2. Qinba State Key Laboratory of Biological Resources and Ecological Environment, Shaanxi University of Technology, Hanzhong, Shaanxi, China.
3. Department of Biology, QinLing-Bashan Mountains Bioresources Comprehensive Development C. I. C., Shaanxi University of Technology, 723001 Hanzhong, China.
4. Shaanxi Province Key Laboratory of Bio-resources, Shaanxi University of Technology, Hanzhong, Shaanxi, China.
5. Affiliated 3201 Hospital of genertec Universal MedicalGroup Company Limited, Hanzhong 723000, China.
* These authors contributed equally to this work.
Breast cancer has the characteristics of high metastasis and recurrence and ranks first in incidence and mortality among female malignant tumors. Shc SH2-domain binding protein 1 (SHCBP1) is an important protein in intracellular signal transduction and cell division, but the role of SHCBP1 in breast cancers remains elusive. Here, we found that SHCBP1 deficiency inhibited the proliferation of breast cancer cells. Mechanistically, SHCPB1 significantly downregulates the mRNA level of CXCL2, which in turn activates the AKT and ERK signaling, while inactivates the p21 and p27 signaling. In addition, overexpression of SHCPB1 downregulates the protein levels of p21 and p27, which could be completely reversed by restoration of CXCL2 expression. Moreover, we analyzed the expression of both SHCPB1 and CXCL2, and found that SHCPB1 is highly expressed in breast cancer cells or tissues from breast cancer patients compared to normal breast cells or adjacent normal tissues, while CXCL2 is lowly expressed in breast cancer cells or tissues. Collectively, our study reveals that SHCBP1 plays an oncogenic role in breast cancer tumorigenesis partially through inhibiting the inflammatory response and ultimately activating the proliferation of breast cancers.
Keywords: Breast cancer, SHCBP1, MCF-7 cells, CXCL2, Inflammation