The role of TROP-2 in proliferation, survival and clonogenity of breast cancer cells

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NEHYBOVÁ Tereza BENEŠ Petr KNOPFOVÁ Lucia REMŠÍK Ján FEDR Radek SOUČEK Karel ŠMARDA Jan

Rok publikování 2015
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Popis Trop-2 is a cell surface transmembrane glycoprotein encoded by the intronless TACSTD2 gene. It is an intracellular calcium signal transducer that has been first identified as an biomarker for trofoblast cells, invasive cells from blastocyst. Trop-2 has multifaceted role during development and tumorigenesis, including regulation cell proliferation, migration, self-renewal and maintenance of basement membrane integrity. Increased expression of Trop-2 was associated with poor prognosis and metastasis in many cancer types but the data remain controversial. While in the lung adenocarcinoma and squamous cell carcinoma, a negative correlation between Trop-2 expression and metastasis/prognosis was observed, the opposite finding has been frequently reported in other epithelial cancers including prostate, colon, ovarian, gastric and breast. These controversial observations are paralleled by studies in various cancer cell line models suggesting a context-dependent function of Trop-2 during tumorigenesis. The main objective of this study was to analyze the molecular basis of Trop-2 expression, signalling and function in breast cancer cells under various conditions of tumor-like microenvironment. We found that Trop-2 affects proliferation, clonogenic capacity and survival of breast cancer cells. Moreover, we identified JNK/AP-1 signaling as an important regulator of Trop2 expression/function in these cells as well. We believe that understanding the mechanisms underlying Trop-2 function in tumor development and progression may further support the use of Trop-2 as prognostic marker and therapeutic target in solid tumors.
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