B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling

Sreekumar, Amulya; Lu, Michelle; Choudhury, Biswa; Pan, Tien-chi; Pant, Dhruv K.; Lawrence-Paul, Matthew R.; Sterner, Christopher J.; Belka, George K.; Toriumi, Takashi; Benz, Brian A.; Escobar-Aguirre, Matias; Marino, Francesco E.; Esko, Jeffrey D.; Chodosh, Lewis A.

doi:10.1016/j.ccell.2023.11.008

Cancer Cell

2024

DOI: 10.1016/j.ccell.2023.11.008

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B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling

Amulya Sreekumar,

Michelle Lu,

Biswa Choudhury

et al.

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Cited by 5 publications

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Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Mongiat,

Pascal,

Poletto

et al. 2024

Proteoglycan Research

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Antiangiogenic therapy is an established method for the treatment of several cancers and vascular‐related diseases. Most of the agents employed target the vascular endothelial growth factor A, the major cytokine stimulating angiogenesis. However, the efficacy of these treatments is limited by the onset of drug resistance. Therefore, it is of fundamental importance to better understand the mechanisms that regulate angiogenesis and the microenvironmental cues that play significant role and influence patient treatment and outcome. In this context, here we review the importance of the three basement membrane (BM) heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin, and collagen XVIII. These HSPGs are abundantly expressed in the vasculature and, due to their complex molecular architecture, they interact with multiple endothelial cell receptors, deeply affecting their function. Under normal conditions, these proteoglycans exert proangiogenic functions. However, in pathological conditions such as cancer and inflammation, extracellular matrix remodeling leads to the degradation of these large precursor molecules and the liberation of bioactive processed fragments displaying potent angiostatic activity. These unexpected functions have been demonstrated for the C‐terminal fragments of perlecan and collagen XVIII, endorepellin, and endostatin. These bioactive fragments can also induce autophagy in vascular endothelial cells which contributes to angiostasis. Overall, BM proteoglycans deeply affect angiogenesis counterbalancing proangiogenic signals during tumor progression and represent possible means to develop new prognostic biomarkers and novel therapeutic approaches for the treatment of solid tumors.

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Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Mongiat,

Pascal,

Poletto

et al. 2024

Proteoglycan Research

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show abstract

Sweet dreams: glycosylation controls tumor cell dormancy

Bresnahan,

Bravo-Cordero

2024

Trends in Cancer

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Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

Dwyer,

Ruth,

Seidel

et al. 2024

Breast Cancer Res

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B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling

Cited by 5 publications

References 81 publications

Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Sweet dreams: glycosylation controls tumor cell dormancy

Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

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