KANK1 promotes breast cancer development by compromising Scribble-mediated Hippo activation

Shiny Shengzhen Guo (), Zhiying Liu, Guan M. Wang, Zhiqi Sun, Kaikai Yu, James P. Fawcett, Reinhard Buettner, Bo Gao and Reinhard Fässler
Additional contact information
Shiny Shengzhen Guo: Max Planck Institute of Biochemistry
Zhiying Liu: The University of Hong Kong
Guan M. Wang: Max Planck Institute of Biochemistry
Zhiqi Sun: Max Planck Institute of Biochemistry
Kaikai Yu: Max Planck Institute of Biochemistry
James P. Fawcett: Dalhousie University
Reinhard Buettner: University Cologne
Bo Gao: The University of Hong Kong
Reinhard Fässler: Max Planck Institute of Biochemistry

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract KANK1 is expressed in epithelial cells and connects focal adhesions with the adjacent cortical microtubule stabilizing complex. Although KANK1 was shown to suppress cancer cell growth in vitro, TCGA database points to high KANK1 levels associated with poor prognosis in a wide spectrum of human malignancies. Here, we address this discrepancy and report that KANK1 promotes proliferation and survival of PyMT-transformed mammary tumor cells in vivo. Mechanistically, KANK1 localizes to the basal side of basement membrane (BM)-attached transformed luminal epithelial cells. When these cells lose the contact with the BM and disassemble integrin adhesions, KANK1 is found at cell-cell junctions where it competes with the polarity and tumor suppressor Scribble for NOS1AP binding, which curbs the ability of Scribble to promote Hippo pathway activity. The consequences are stabilization and nuclear accumulation of TAZ, growth and survival of tumor cells and elevated breast cancer development.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54645-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54645-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54645-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().