Biology subjects

Sadeghi, N.

Publications and source records attributed to Sadeghi, N..

3 recordsLinked to original sources

bioRxiv2026

Rewiring of EGFR oncogenic program by opposing actions of membrane versus soluble CD109 in HNSCC

The epidermal growth factor receptor (EGFR) expression is often dysregulated in head and neck squamous cell carcinoma (HNSCC), driving cancer cell proliferation, invasion, and metastasis through diverse pathways, thereby contributing to aggressive chemo- and radio-therapy resistance. A GPI-anchored protein, CD109 is upregulated in multiple cancers, including HNSCC. While membrane-anchored CD109 (mCD109) is pro-tumorigenic in SCC via EGFR/STAT3 activation, the role of protease-cleaved soluble CD109 (sCD109) is poorly understood. Our groundbreaking findings demonstrate that sCD109 antagonizes EGFR signaling by directly binding to the EGFR extracellular domain, preventing mCD109-EGFR stabilizing interactions on the cell surface, followed by inhibition of EGFR phosphorylation at Y1068 and downstream signaling cascades (AKT, MAPK, and STAT3) consequently suppressing cancer cell migration, invasion, 3D tumor spheroid formation and angiogenic tube formation. In addition, we found that sCD109 regulates EGFR fates by inhibiting nuclear localization of phosphorylated EGFR and promoting EGFR degradation. Additionally, sCD109 significantly reduces EGF-induced expression of cancer stem cell markers (CD44 and CD133) and embryonic stem cell markers (Nanog and Sox2), suggesting a suppressive role in cancer stemness. Taken together, these results underscore the opposing roles of mCD109 and sCD109: with sCD109 acting as an antagonist by inhibiting mCD109/EGFR-driven oncogenic signaling and phenotypes. Our current findings reveal a complex interplay among mCD109, sCD109, and EGFR, identifying a mechanism for targeting EGFRs degradation in HNSCC, and lay the groundwork for future research on investigating sCD109s modulatory role in preclinical models of HNSCC.

Cancer Biology↗

bioRxiv2021

Spectro-temporal neural dynamics during sentence completion

This magnetoencephalography (MEG) study aimed at characterizing the spectro-temporal dynamics of brain oscillatory activity elicited by sentence completion (SC). For that purpose, we adapted a version of the SC experimental paradigm typically used in functional magnetic resonance imaging to MEG investigation constraints. Twenty right-handed healthy young adults underwent MEG recordings while they were sequentially presented with short sentences divided in three parts: the first two giving context and the last requiring completion. MEG data were then analysed using a prior-free, non-parametric statistical approach with stringent control of the family-wise error rate. We identified three successive significant neural response patterns associated with distinct spatial and spectro-temporal characteristics: (i) an early (<300 ms) bioccipital 4-10-Hz event-related synchronization (ERS); (ii) an intermediate (at about 400 ms) 8-30-Hz event-related desynchronization (ERD) in an extended semantic network involving the ventral language stream as well as bilateral posterior nodes of the default mode network (DMN) in both hemispheres; (iii) a late (>800 ms) 8-30 Hz ERD involving the left dorsal language stream. Furthermore, the left component of the ventral language stream displayed prolonged ERD after 800 ms compared to the right which showed signs of inhibition in the form of ERS. Overall, this study elucidates the dynamics of the recruitment of the language network that accompany SC and the spectro-temporal signature of an extended semantic network. This MEG adaptation of an SC paradigm also paves the way for novel approaches in presurgical language mapping and may help to understand the neural underpinnings of the alterations of sentence completion in various neurologic disorders affecting language.

neuroscience↗

bioRxiv2021

Alpha peak frequency is linked to episodic memory impairment in pathological aging

The Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimers disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 minutes of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients encoding efficiency as well as with the efficacy of semantic cues in facilitating patients retrieval of previous stored word. The APF also correlated positively with patients hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.

neuroscience↗