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Fibronectin acts as a molecular switch to determine SPARC function in pancreatic cancer.

Abstract：

:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of all solid tumours and more effective therapy is urgently needed. The stroma is thought to play a critical role in tumour development and metastasis, and high stromal expression of the matricellular protein SPARC has been robustly associated with poor patient prognosis. However, the precise role of SPARC has been highly controversial, with multiple studies demonstrating tumour-suppressor properties of this protein in vitro. This conflicting data has been a barrier to the development of new therapeutic approaches targeting SPARC, despite current interest in stromal-therapy. We show conclusively that SPARC acts directly on cancer cells to promote pancreatic cancer cell proliferation. This contradicts previous in vitro studies, but is consistent with the observed clinical association between SPARC expression and poor patient prognosis. However, depletion of fibronectin switches the activity of SPARC from promoting cancer cell proliferation to growth inhibition and induction of apoptosis. Thus, targeting the interaction between SPARC and fibronectin could be used to turn the highly expressed tumour protein SPARC against the tumour to induce tumour cytotoxicity, and is a novel target for PDAC therapy.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Munasinghe A,Malik K,Mohamedi F,Moaraf S,Kocher H,Jones L,Hill NJ

doi

10.1016/j.canlet.2020.02.031

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

88-96

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(20)30100-2

journal_volume

477

pub_type

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