Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1

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Tvingsholm , S A , Hansen , M B , Clemmensen , K K B , Brix , D M , Rafn , B , Frankel , L B , Louhimo , R , Moreira , J , Hautaniemi , S , Gromova , I , Jäättelä , M & Kallunki , T 2018 , ' Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1 ' , Oncogenesis , vol. 7 , 14 . https://doi.org/10.1038/s41389-017-0014-6

Title: Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1
Author: Tvingsholm, Siri Amanda; Hansen, Malene Bredahl; Clemmensen, Knut Kristoffer Bundgaard; Brix, Ditte Marie; Rafn, Bo; Frankel, Lisa B.; Louhimo, Riku; Moreira, Jose; Hautaniemi, Sampsa; Gromova, Irina; Jäättelä, Marja; Kallunki, Tuula
Other contributor: University of Helsinki, Genome-Scale Biology (GSB) Research Program
University of Helsinki, Research Programs Unit






Date: 2018-02
Language: eng
Number of pages: 15
Belongs to series: Oncogenesis
ISSN: 2157-9024
DOI: https://doi.org/10.1038/s41389-017-0014-6
URI: http://hdl.handle.net/10138/234638
Abstract: Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. Analysis of primary breast cancer tissues reveals a gradual upregulation of MZF1 from normal breast epithelium to invasive ductal carcinoma and a negative correlation between several let-7 family members and MZF1 mRNA, suggesting that the inverse regulatory relationship between let-7 and MZF1 may play a role in the development of invasive breast cancer. Furthermore, we show that MZF1 regulates lysosome trafficking in ErbB2-positive breast cancer cells. In line with this, MZF1 depletion or let-7 expression inhibits invasion-promoting anterograde trafficking of lysosomes and invasion of ErbB2-expressing MCF7 spheres. The results presented here link MZF1 and let-7 to lysosomal processes in ErbB2-positive breast cancer cells that in non-cancerous cells have primarily been connected to the transcription factor EB. Identifying MZF1 and let-7 as regulators of lysosome distribution in invasive breast cancer cells, uncouples cancer-associated, invasion-promoting lysosomal alterations from normal lysosomal functions and thus opens up new possibilities for the therapeutic targeting of cancer lysosomes.
Subject: BREAST-CANCER CELLS
CYSTEINE CATHEPSINS
GENE-EXPRESSION
METASTASIS
MZF-1
PROGRESSION
DIFFERENTIATION
TRANSFORMATION
BIOGENESIS
KINASE
3122 Cancers
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