S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

Abstract

BACKGROUND: High levels of S100A6 have been associated with poor outcome in pancreatic cancer patients. The functional role of S100A6 is, however, poorly understood. METHODS: Immunoprecipitation followed by two-dimensional gel electrophoresis and mass spectrometry were undertaken to identify S100A6 interacting proteins in pancreatic cancer cells. Immunohistochemistry and coimmunofluorescence were performed to examine expression or colocalisation of proteins. siRNA was used to deplete specific proteins and effects on motility were measured using Boyden Chamber and wound healing assays. RESULTS: Our proteomic screen to identify S100A6 interacting proteins revealed annexin 11, annexin 2, tropomyosin b and a candidate novel interactor lamin B1. Of these, annexin 2 was considered particularly interesting, as, like S100A6, it is expressed early in the development of pancreatic cancer and overexpression occurs with high frequency in invasive cancer. Reciprocal immunoprecipitation confirmed the interaction between annexin 2 and S100A6 and the proteins colocalised, particularly in the plasma membrane of cultured pancreatic cancer cells and primary pancreatic tumour tissue. Analysis of primary pancreatic cancer specimens (n ¼ 55) revealed a strong association between high levels of cytoplasmic S100A6 and the presence of annexin 2 in the plasma membrane of cancer cells (P ¼ 0.009). Depletion of S100A6 was accompanied by diminished levels of membrane annexin 2 and caused a pronounced reduction in the motility of pancreatic cancer cells. CONCLUSION: These findings point towards a functional role for S100A6 that may help explain the link between S100A6 expression in pancreatic cancer and aggressive disease.

MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer

“…47 In this context, interactions with tumor associated proteins such as annexin A2 and p53 may indicate a role of S100-A6 in cancer progression and metastasis. 48,49 Indeed, increased levels of S100-A6 have been found to be associated with metastasis or survival in colon and pancreatic cancer, respectively. 50,51 Similarly, our study showed a significant correlation of S100-A6 expression with clinical parameters such as regional lymph node metastasis, distant metastasis, tumor cell differentiation, and prognosis.…”

S100A6 Overexpression Is Associated with Poor Prognosis and Is Epigenetically Up-Regulated in Gastric Cancer

“…34 In addition, Nedjadi et al suggested S100A6 can interact with the annexin 2 and then promotes pancreatic cancer cell motility. 35 Therefore, these interactions may play an important role in cancer metastasis.…”

ANXA2 Regulates the Behavior of SGC-7901 Cells

“…The excessive expression of ANXA2 was reported to enhance the malignancy of numerous cancers in digestion system (Emoto et al, 2001;Esposito et al, 2006;Mohammad et al, 2008;Nedjadi et al, 2009).…”