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- Dingemanse, M., et al.
(author)
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Beyond Single-Mindedness: A Figure-Ground Reversal for the Cognitive Sciences
- 2023
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In: Cognitive Science. - : Wiley. - 0364-0213 .- 1551-6709. ; 47:1
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Journal article (peer-reviewed)abstract
- A fundamental fact about human minds is that they are never truly alone: all minds are steeped in situated interaction. That social interaction matters is recognized by any experimentalist who seeks to exclude its influence by studying individuals in isolation. On this view, interaction complicates cognition. Here, we explore the more radical stance that interaction co-constitutes cognition: that we benefit from looking beyond single minds toward cognition as a process involving interacting minds. All around the cognitive sciences, there are approaches that put interaction center stage. Their diverse and pluralistic origins may obscure the fact that collectively, they harbor insights and methods that can respecify foundational assumptions and fuel novel interdisciplinary work. What might the cognitive sciences gain from stronger interactional foundations? This represents, we believe, one of the key questions for the future. Writing as a transdisciplinary collective assembled from across the classic cognitive science hexagon and beyond, we highlight the opportunity for a figure-ground reversal that puts interaction at the heart of cognition. The interactive stance is a way of seeing that deserves to be a key part of the conceptual toolkit of cognitive scientists.
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| 2. |
- Guerra, Emanuela, et al.
(author)
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Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer
- 2021
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In: Neoplasia. - : Elsevier Science INC. - 1522-8002 .- 1476-5586. ; 23:9, s. 898-911
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Journal article (peer-reviewed)abstract
- We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAMIO underlies Trop-2-driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated Delta cytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from beta-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of beta-catenin signaling, which were further enhanced by the Delta cytoTrop-2 mutant. This Trop-2/E-cadherin/beta-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2-centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.
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