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Periostin blockade overcomes chemoresistance via restricting the expansion of mesenchymal tumor subpopulations in breast cancer.

Abstract：

:Recent studies suggest a functional involvement of Epithelial-Mesenchymal Transition (EMT) in tumor chemoresistance. Specifically, EMT is associated with chemoresistance and poor prognosis in triple-negative breast cancer. However, no effective therapy targeting EMT has been developed. Here, we report that periostin, an extracellular matrix protein, was induced upon chemotherapy and tightly correlated with the EMT gene signature and poor prognosis in breast cancer. In triple-negative breast cancer xenografts, chemotherapy upregulated periostin expression in tumor cells, triggered expansion of mesenchymal tumor cells and promoted invasion in residual tumors. Knockdown of periostin inhibited outgrowth and invasion of mesenchymal tumor cells upon chemotherapy. Furthermore, chemotherapy upregulated cancer-specific variants of periostin and application of a blocking antibody specifically targeting those variants overcame chemoresistance and halted disease progression without toxicity. Together, these data indicate that periostin plays a key role in EMT-dependent chemoresistance and is a promising target to overcome chemoresistance in triple-negative breast cancer.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Nakazawa Y,Taniyama Y,Sanada F,Morishita R,Nakamori S,Morimoto K,Yeung KT,Yang J

doi

10.1038/s41598-018-22340-7

subject

Has Abstract

pub_date

2018-03-05 00:00:00

pages

4013

issue

1

issn

2045-2322

pii

10.1038/s41598-018-22340-7

journal_volume

8

pub_type

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