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Galectin-9 Signaling Drives Breast Cancer Invasion through Extracellular Matrix

Pally, Dharma ; Banerjee, Mallar ; Hussain, Shahid ; Kumar, Rekha V ; Petersson, Alexandra LU ; Rosendal, Ebba ; Gunnarsson, Ludvig ; Peterson, Kristoffer LU ; Leffler, Hakon LU and Nilsson, Ulf J LU , et al. (2022) In ACS Chemical Biology 17(6). p.1376-1386
Abstract

Aberrations in glycan and lectin expression and function represent one of the earliest hallmarks of cancer. Among galectins, a conserved family of β-galactoside-binding lectins, the role of Galectin-9 in immune-tumor interactions is well-established, although its effect on cancer cell behavior remains unclear. In this study, we assayed for, and observed, an association between Galectin-9 expression and invasiveness of breast cancer cells in vitro and in vivo. Genetic perturbation and pharmacological inhibition using novel cognate inhibitors confirmed a positive correlation between Galectin-9 levels and the adhesion of invasive cancer cells to─and their invasion through─constituted organomimetic extracellular matrix microenvironments.... (More)

Aberrations in glycan and lectin expression and function represent one of the earliest hallmarks of cancer. Among galectins, a conserved family of β-galactoside-binding lectins, the role of Galectin-9 in immune-tumor interactions is well-established, although its effect on cancer cell behavior remains unclear. In this study, we assayed for, and observed, an association between Galectin-9 expression and invasiveness of breast cancer cells in vitro and in vivo. Genetic perturbation and pharmacological inhibition using novel cognate inhibitors confirmed a positive correlation between Galectin-9 levels and the adhesion of invasive cancer cells to─and their invasion through─constituted organomimetic extracellular matrix microenvironments. Signaling experiments and unbiased quantitative proteomics revealed Galectin-9 induction of Focal Adhesion Kinase activity and S100A4 expression, respectively. FAK inhibition decreased S100A4 mRNA levels. Our results provide crucial insights into how elevated Galectin-9 expression potentiates the invasiveness of breast cancer cells during early steps of invasion.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Chemical Biology
volume
17
issue
6
pages
1376 - 1386
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85132452079
  • pmid:35605245
ISSN
1554-8937
DOI
10.1021/acschembio.1c00902
language
English
LU publication?
yes
id
87183f5a-195f-49d9-8cc4-fa67ebb9e837
date added to LUP
2022-05-31 11:37:01
date last changed
2024-04-15 12:54:31
@article{87183f5a-195f-49d9-8cc4-fa67ebb9e837,
  abstract     = {{<p>Aberrations in glycan and lectin expression and function represent one of the earliest hallmarks of cancer. Among galectins, a conserved family of β-galactoside-binding lectins, the role of Galectin-9 in immune-tumor interactions is well-established, although its effect on cancer cell behavior remains unclear. In this study, we assayed for, and observed, an association between Galectin-9 expression and invasiveness of breast cancer cells in vitro and in vivo. Genetic perturbation and pharmacological inhibition using novel cognate inhibitors confirmed a positive correlation between Galectin-9 levels and the adhesion of invasive cancer cells to─and their invasion through─constituted organomimetic extracellular matrix microenvironments. Signaling experiments and unbiased quantitative proteomics revealed Galectin-9 induction of Focal Adhesion Kinase activity and S100A4 expression, respectively. FAK inhibition decreased S100A4 mRNA levels. Our results provide crucial insights into how elevated Galectin-9 expression potentiates the invasiveness of breast cancer cells during early steps of invasion.</p>}},
  author       = {{Pally, Dharma and Banerjee, Mallar and Hussain, Shahid and Kumar, Rekha V and Petersson, Alexandra and Rosendal, Ebba and Gunnarsson, Ludvig and Peterson, Kristoffer and Leffler, Hakon and Nilsson, Ulf J and Bhat, Ramray}},
  issn         = {{1554-8937}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  pages        = {{1376--1386}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Chemical Biology}},
  title        = {{Galectin-9 Signaling Drives Breast Cancer Invasion through Extracellular Matrix}},
  url          = {{http://dx.doi.org/10.1021/acschembio.1c00902}},
  doi          = {{10.1021/acschembio.1c00902}},
  volume       = {{17}},
  year         = {{2022}},
}