Abstract Number: PB2133
Meeting: ISTH 2020 Congress
Background: Intracellular calcium ions act as second messengers regulating numerous physiological functions. Alterations in calcium signalling have also been implicated in several pathological conditions including cancer.
Aims: To determine whether MUC1, a well-established tumor marker, plays a role in modulating calcium signalling and thereby alters the procoagulant properties of cancer cells.
Methods: MUC1 knockdown breast cancer MCF-7 cells were used to investigate whether the overexpression of MUC1 by cancer cells has an influence on calcium signalling pathways, as determined by analysis of the level of calcium signalling proteins, the degree of intracellular calcium mobilization, and calcium-induced cellular effects. The investigation was extended to normal human mammary epithelial, breast and pancreatic cancer cell lines, expressing different levels of MUC1.
Results: MUC1 downregulation in MCF-7 cancer cells was associated with aberrant expression of several calcium transporter proteins. In addition, the level of each of these calcium signalling pathway proteins was correlated with MUC1 levels in normal human mammary epithelial and human breast and pancreatic cancer cell lines. As a consequence, a number of proteins whose activities are calcium dependent, such as p-CaMKII, and procoagulant proteins Va, Xa and thrombin, were reduced in MUC1 downregulated MCF-7 cells. Moreover, PAR-1 and PAR-4 cleavage by thrombin as well as the resultant calcium mobilization were also reduced in MUC1 downregulated MCF-7 cells.
Conclusions: The downregulation of MUC1 is capable of modulating calcium cellular effects via altered expression of calcium signalling proteins as well as calcium mobilization in human cancer cells and associated procoagulant activity. Such properties contribute to a crucial role for MUC1 in numerous signalling networks within tumorigenesis. These findings suggest a potential role for MUC1 through modulation of Ca2+ signalling in cancer, which may help guide the development of therapeutic targeting of MUC1.
To cite this abstract in AMA style:Chen Y, Scully M. The Downregulation of Mucin1 Initiates Aberrant Calcium Signalling Pathways of Cancer Cells which Are Partly Responsible for the Procoagulant Phenotype [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-downregulation-of-mucin1-initiates-aberrant-calcium-signalling-pathways-of-cancer-cells-which-are-partly-responsible-for-the-procoagulant-phenotype/. Accessed February 27, 2024.
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