S100A14 Interacts with S100A16 and Regulates Its Expression in Human Cancer Cells

Abstract

Both S100A14 and S100A16 are members of the multifunctional S100 protein family. Formation of homo/heterodimers is considered to be one of the major mechanisms for S100 proteins to execute their diverse cellular functions. By employing a classical Yeast two hybrid (Y-2 H) screen, we identified S100A16 as the single interaction partner of S100A14. This interaction was verified by co-immunoprecipitation, double indirect immunofluorescence and double immunostaining in specimens of oral squamous cell carcinoma and normal oral mucosa. The functional significance of this interaction was examined by employing retroviral mediated over-expression and knock-down of these proteins in several cancer cell-lines. Over-expression and knock-down of S100A14 led to concomitant up- and down-regulation of S100A16 protein in the cell-lines examined. However, there was no up-regulation of S100A16 mRNA upon S100A14 over-expression, indicating that modulation of S100A16 expression was not due to enhanced transcriptional activity but possibly by post-transcriptional regulation. In contrary, over-expression of S100A16 was associated neither with the up-regulation of S100A14 mRNA nor its protein, suggesting a unidirectional regulation between S100A14 and S100A16. Cellular treatment with protein synthesis inhibitor cycloheximide demonstrated a time-dependent intracellular degradation of both S100A16 and S100A14 proteins. Additionally, regulation of S100A16 and S100A14 degradation was found to be independent of the classical proteasomal and lysosomal pathways of protein degradation. Further studies will therefore be necessary to understand the functional significance of this interaction and the mechanisms on how S100A14 is involved in the regulation of S100A16 expression.

Brain microvascular endothelial cell exosome–mediated S100A16 up‐regulation confers small‐cell lung cancer cell survival in brain

“…The elevation of S100A16 induced by HBMEC exosomes facilitated the survival of SCLC cells It has been reported that S100A16 is up-regulated in several cancer tissues, suggesting a function related to malignant transformation or tumor development (14)(15)(16). Our results from the above clinical data indicate that the elevation of S100A16 was associated with SCLC metastasis to the brain.…”

“…The coexpression of S100A16 and S100A14 has been associated with a poor prognosis in patients with breast cancer. These protein interactions could promote the invasive activity of breast cancer cells via an interaction with cytoskeleton dynamics (15). In addition, the up-regulation of S100A16 promoted epithelial-mesenchymal transition via the Notch1 pathway in the breast cancer cell line MCF-7 (16).…”

S100A16 is a prognostic marker for colorectal cancer

“…Compared to S100A16, S100A14, another member of the S100 family, has been studied in more depth. S100A14 was shown to be the sole interaction partner of S100A16 in OSCC . In addition, genome‐wide functional coupling networks database also showed that S100A16 was the main partner of the S100A14 protein .…”

S100A16suppresses the growth and survival of leukaemia cells and correlates with relapse and relapse free survival in adults with Philadelphia chromosome‐negative B‐cell acute lymphoblastic leukaemia

“…Abnormal expression of S100A16 was found in many tumours, such as cancer of the breast cancer, prostate and lung, suggesting a function related to malignant transformation or tumour development (Marenholz & Heizmann, ). For example, the co‐expression of S100A14 and S100A16 correlated with a poor prognosis in human breast cancer and promoted the invasive activity of breast cancer cells via an interaction with cytoskeletal dynamics (Sapkota et al , ). High S100A16 expression was found to be significantly associated with a poor prognosis in lung, prostate and breast cancers (Saito et al , ).…”