Biology subjects

Antkowiak, M.

Publications and source records attributed to Antkowiak, M..

3 recordsLinked to original sources

bioRxiv2025

Single Nuclei-Derived Molecular Subtypes of Gastrointestinal Stromal Tumors Correlate with Clinicopathologic Features and Predict Clinical Outcomes

Historically, gastrointestinal stromal tumor (GIST) has been subtyped by oncogenic driver mutations. However, tumors with the same mutational profile can have variable biology. To further explore the impact of molecular diversity on GIST biology, we performed single nucleus RNA sequencing on 16 primary GIST and utilized an integrated single cell atlas of the normal GI tract composed from multiple publicly available datasets to identify six distinct GIST cell states. We then statistically estimated the relative abundances of these profiles in bulk transcriptomic data. These were used to define six common GIST molecular subtypes based upon one or two predominant tumor cell states. We found that these molecular subtypes correlate with tumor locations, mutational profiles, and patient outcomes, and validated these subtypes in an independent international cohort. These molecular subtypes have the potential to be used for clinical prognostication for patients with GIST, identifying new therapeutic targets, and studying the cell of transformation of GIST.

cancer biology↗

bioRxiv2020

Condensation of pericentrin proteins in human cells illuminates phase separation in centrosome assembly

AbstractAt the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. We found that endogenously expressed pericentrin (PCNT), a conserved PCM scaffold protein, condenses into dynamic granules during late G2/early mitosis before incorporating into mitotic centrosomes. Furthermore, the N-terminal portion of PCNT--enriched with conserved coiled-coils (CCs) and low-complexity regions (LCRs)--phase separates into dynamic condensates that selectively recruit PCM proteins and nucleate microtubules in cells. We propose that CCs and LCRs, two prevalent sequence features in the centrosomal proteome, are preserved under evolutionary pressure in part to mediate liquid-liquid phase separation, a process that bestows upon the centrosome distinct properties critical for its assembly and functions.

cell biology↗

bioRxiv2017

Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near the centrosome, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism.

cell biology↗