Biology subjects

Kantar, D.

Publications and source records attributed to Kantar, D..

4 recordsLinked to original sources

bioRxiv2026

Mitochondrial inner membrane interactors of Aurora kinase A/AURKA and PHB2 shape organelle metabolic heterogeneity.

Mitochondria support tumor growth by flexibly rewiring their own activity. Yet, how signaling networks organize this metabolic diversity across and within cells remains poorly understood. Here, we uncover a platform of inner mitochondrial membrane proteins that couple Aurora kinase A (AURKA) and the mitophagy receptor Prohibitin-2 (PHB2) to the local control of ATP production and organelle architecture. Using proximity interactomics and live-cell FRET/FLIM microscopy, we identify NDUFA9, ATP5F1A/B, SAMM50, and SLC25A13 as shared AURKA/PHB2 interactors positioned at respiratory chain and cristae-maintaining sites. We show that AURKA overexpression profoundly rewires the interactomes of NDUFA9 and ATP5F1A without disrupting their nanoscale proximity in the inner membrane, and reshapes mitochondrial morphology while preserving these signaling hubs. The AURKA/PHB2-targeting compound HMBB restores NDUFA9 and ATP5F1A interactomes, indicating that these complexes act as key nodes for AURKA-dependent metabolic adaptation at the population level. Finally, single-cell FRET microscopy coupled to super-resolution imaging reveals that SLC25A13 is required to sustain AURKA-induced metabolic heterogeneity within individual cancer cells. Our work links a multifunctional kinase, a mitophagy receptor, and respiratory complexes into a common inner membrane platform that spatially drives mitochondrial heterogeneity, with implications for metabolism-focused anticancer strategies.

cell biology↗

bioRxiv2023

The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in HCT116 colon cancer cells

YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the P73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using several colorectal cancer cell lines, we show here that oxaliplatin treatment led to a dramatic core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of P73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed an antagonistic with oxaliplatin in co-treatments. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and P53 activity pushes cells towards apoptosis.

cancer biology↗

bioRxiv2020

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.

cancer biology↗

bioRxiv2020

Loss of epithelial polarity redirects Notch signaling and triggers a Xrp1 response during neoplastic growth in Drosophila

Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.

developmental biology↗