Galectin-9 Signaling Drives Breast Cancer Invasion through Extracellular Matrix
(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.
(Less)
- author
- organization
- publishing date
- 2022-05-23
- 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
- 2024-10-30 09:32:31
@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}}, }