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

Research output: Contribution to journalJournal articleResearchpeer-review

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Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1. / Tvingsholm, Siri Amanda; Hansen, Malene Bredahl; Clemmensen, Knut Kristoffer Bundgaard; Brix, Ditte Marie; Rafn, Bo; Frankel, Lisa B.; Louhimo, Riku; Moreira, José; Hautaniemi, Sampsa; Gromova, Irina; Jäättelä, Marja; Kallunki, Tuula.

In: Oncogene, Vol. 7, No. 2, 14, 2018, p. 1-15.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Tvingsholm, SA, Hansen, MB, Clemmensen, KKB, Brix, DM, Rafn, B, Frankel, LB, 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', Oncogene, vol. 7, no. 2, 14, pp. 1-15. https://doi.org/10.1038/s41389-017-0014-6

APA

Tvingsholm, S. A., Hansen, M. B., Clemmensen, K. K. B., Brix, D. M., Rafn, B., Frankel, L. B., ... Kallunki, T. (2018). Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1. Oncogene, 7(2), 1-15. [14]. https://doi.org/10.1038/s41389-017-0014-6

Vancouver

Tvingsholm SA, Hansen MB, Clemmensen KKB, Brix DM, Rafn B, Frankel LB et al. Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1. Oncogene. 2018;7(2):1-15. 14. https://doi.org/10.1038/s41389-017-0014-6

Author

Tvingsholm, Siri Amanda ; Hansen, Malene Bredahl ; Clemmensen, Knut Kristoffer Bundgaard ; Brix, Ditte Marie ; Rafn, Bo ; Frankel, Lisa B. ; Louhimo, Riku ; Moreira, José ; Hautaniemi, Sampsa ; Gromova, Irina ; Jäättelä, Marja ; Kallunki, Tuula. / Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1. In: Oncogene. 2018 ; Vol. 7, No. 2. pp. 1-15.

Bibtex

@article{1962a1f1b71b44f190ba9215791bb78b,
title = "Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1",
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.",
author = "Tvingsholm, {Siri Amanda} and Hansen, {Malene Bredahl} and Clemmensen, {Knut Kristoffer Bundgaard} and Brix, {Ditte Marie} and Bo Rafn and Frankel, {Lisa B.} and Riku Louhimo and Jos{\'e} Moreira and Sampsa Hautaniemi and Irina Gromova and Marja J{\"a}{\"a}ttel{\"a} and Tuula Kallunki",
year = "2018",
doi = "10.1038/s41389-017-0014-6",
language = "English",
volume = "7",
pages = "1--15",
journal = "Oncogene",
issn = "0950-9232",
publisher = "nature publishing group",
number = "2",

}

RIS

TY - JOUR

T1 - Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1

AU - Tvingsholm, Siri Amanda

AU - Hansen, Malene Bredahl

AU - Clemmensen, Knut Kristoffer Bundgaard

AU - Brix, Ditte Marie

AU - Rafn, Bo

AU - Frankel, Lisa B.

AU - Louhimo, Riku

AU - Moreira, José

AU - Hautaniemi, Sampsa

AU - Gromova, Irina

AU - Jäättelä, Marja

AU - Kallunki, Tuula

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41389-017-0014-6

DO - 10.1038/s41389-017-0014-6

M3 - Journal article

C2 - 29396433

AN - SCOPUS:85041561580

VL - 7

SP - 1

EP - 15

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 2

M1 - 14

ER -

ID: 211815206