AACR Presentations

Recent Mercurio Lab work was a part of two presentations at the annual American Association for Cancer Research meeting.

Graduate student Emmet Karner presented on ferroptosis resistance in epithelial populations of TNBCs mediated by laminin 332 and integrin beta4. His abstract can be found here.

aTyr Pharma presented on our collaborative work highlighting a fully humanized monoclonal antibody targeting the VEGF-NRP2 pathway sensitizing highly aggressive and chemoresistant TNBC subtypes to chemotherapy. Their abstract can be found here.

Mandy's paper on PD-L1 regulation of integrin dynamics is published!

ABSTRACT

Although the immune checkpoint function of PD-L1 has dominated its study, we report that PD-L1 has an unanticipated intrinsic function in promoting the dynamics of persistent cell migration. PD-L1 concentrates at the rear of migrating carcinoma cells where it facilitates retraction, resulting in the formation of PD-L1–containing retraction fibers and migrasomes. PD-L1 promotes retraction by interacting with and localizing the β4 integrin to the rear enabling this integrin to stimulate contractility. This mechanism involves the ability of PD-L1 to maintain cell polarity and lower membrane tension at the cell rear compared with the leading edge that promotes the localized interaction of PD-L1 and the β4 integrin. This interaction enables the β4 integrin to engage the actin cytoskeleton and promote RhoA-mediated contractility. The implications of these findings with respect to cell-autonomous functions of PD-L1 and cancer biology are significant.

Wang M, Xiong C, Mercurio AM. PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics. Journal of Cell Biology. 2022 March 28.

Melanie's paper on O-linked glycosylation defining stem cell populations is published!

ABSTRACT

We pursued the hypothesis that specific glycans can be used to distinguish breast cancer stem cells (CSCs) and influence their function. Comparison of CSCs and non-CSCs from multiple breast cancer models revealed that CSCs are distinguished by expression of α2,3 sialylated core2 O-linked glycans. We identified a lectin, SLBR-N, which binds to O-linked α2,3 sialic acids, that was able to enrich for CSCs in vitro and in vivo. This O-glycan is expressed on CD44 and promotes its interaction with hyaluronic acid, facilitating CD44 signaling and CSC properties. In con- trast, FUT3, which contributes to sialyl Lewis X (sLeX) production, is preferentially expressed in the non-CSC popu- lation, and it antagonizes CSC function. Collectively, our data indicate that SLBR-N can be more efficient at enriching for CSCs than CD44 itself because its use avoids the issues of CD44 splicing and glycan status. These data also reveal how differential glycosylation influences CSC fate.

Walker MR, Goel HL, Mukhopadhyay D, Chhoy P, Karner ER, Clark JL, Liu H, Li R, Zhu JL, Chen S, Mahal LK, Bensing BA, Mercurio AM.  O-linked α2,3 sialylation defines stem cell populations in breast cancer. Science Advances. 2022 January 07. PMID: 34995107