SORLA regulates endosomal trafficking and oncogenic fitness of HER2

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SORLA regulates endosomal trafficking and oncogenic fitness of HER2. / Pietilä, Mika; Sahgal, Pranshu; Peuhu, Emilia; Jäntti, Niklas Z.; Paatero, Ilkka; Närvä, Elisa; Al-Akhrass, Hussein; Lilja, Johanna; Georgiadou, Maria; Andersen, Olav M.; Padzik, Artur; Sihto, Harri; Joensuu, Heikki; Blomqvist, Matias; Saarinen, Irena; Boström, Peter J.; Taimen, Pekka; Ivaska, Johanna.

I: Nature Communications, Bind 10, Nr. 1, 2340, 05.2019, s. 1-16.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Pietilä, M, Sahgal, P, Peuhu, E, Jäntti, NZ, Paatero, I, Närvä, E, Al-Akhrass, H, Lilja, J, Georgiadou, M, Andersen, OM, Padzik, A, Sihto, H, Joensuu, H, Blomqvist, M, Saarinen, I, Boström, PJ, Taimen, P & Ivaska, J 2019, 'SORLA regulates endosomal trafficking and oncogenic fitness of HER2', Nature Communications, bind 10, nr. 1, 2340, s. 1-16. https://doi.org/10.1038/s41467-019-10275-0

APA

Pietilä, M., Sahgal, P., Peuhu, E., Jäntti, N. Z., Paatero, I., Närvä, E., ... Ivaska, J. (2019). SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nature Communications, 10(1), 1-16. [2340]. https://doi.org/10.1038/s41467-019-10275-0

CBE

Pietilä M, Sahgal P, Peuhu E, Jäntti NZ, Paatero I, Närvä E, Al-Akhrass H, Lilja J, Georgiadou M, Andersen OM, Padzik A, Sihto H, Joensuu H, Blomqvist M, Saarinen I, Boström PJ, Taimen P, Ivaska J. 2019. SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nature Communications. 10(1):1-16. https://doi.org/10.1038/s41467-019-10275-0

MLA

Vancouver

Pietilä M, Sahgal P, Peuhu E, Jäntti NZ, Paatero I, Närvä E o.a. SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nature Communications. 2019 maj;10(1):1-16. 2340. https://doi.org/10.1038/s41467-019-10275-0

Author

Pietilä, Mika ; Sahgal, Pranshu ; Peuhu, Emilia ; Jäntti, Niklas Z. ; Paatero, Ilkka ; Närvä, Elisa ; Al-Akhrass, Hussein ; Lilja, Johanna ; Georgiadou, Maria ; Andersen, Olav M. ; Padzik, Artur ; Sihto, Harri ; Joensuu, Heikki ; Blomqvist, Matias ; Saarinen, Irena ; Boström, Peter J. ; Taimen, Pekka ; Ivaska, Johanna. / SORLA regulates endosomal trafficking and oncogenic fitness of HER2. I: Nature Communications. 2019 ; Bind 10, Nr. 1. s. 1-16.

Bibtex

@article{4d11f589c745476ab45f6ef5ed00c335,
title = "SORLA regulates endosomal trafficking and oncogenic fitness of HER2",
abstract = "The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.",
author = "Mika Pietil{\"a} and Pranshu Sahgal and Emilia Peuhu and J{\"a}ntti, {Niklas Z.} and Ilkka Paatero and Elisa N{\"a}rv{\"a} and Hussein Al-Akhrass and Johanna Lilja and Maria Georgiadou and Andersen, {Olav M.} and Artur Padzik and Harri Sihto and Heikki Joensuu and Matias Blomqvist and Irena Saarinen and Bostr{\"o}m, {Peter J.} and Pekka Taimen and Johanna Ivaska",
year = "2019",
month = "5",
doi = "10.1038/s41467-019-10275-0",
language = "English",
volume = "10",
pages = "1--16",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - SORLA regulates endosomal trafficking and oncogenic fitness of HER2

AU - Pietilä, Mika

AU - Sahgal, Pranshu

AU - Peuhu, Emilia

AU - Jäntti, Niklas Z.

AU - Paatero, Ilkka

AU - Närvä, Elisa

AU - Al-Akhrass, Hussein

AU - Lilja, Johanna

AU - Georgiadou, Maria

AU - Andersen, Olav M.

AU - Padzik, Artur

AU - Sihto, Harri

AU - Joensuu, Heikki

AU - Blomqvist, Matias

AU - Saarinen, Irena

AU - Boström, Peter J.

AU - Taimen, Pekka

AU - Ivaska, Johanna

PY - 2019/5

Y1 - 2019/5

N2 - The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.

AB - The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.

UR - http://www.scopus.com/inward/record.url?scp=85066303585&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10275-0

DO - 10.1038/s41467-019-10275-0

M3 - Journal article

VL - 10

SP - 1

EP - 16

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2340

ER -