Biology subjects

shi, y.

Publications and source records attributed to shi, y..

3 recordsLinked to original sources

bioRxiv2022

Chaperone-mediated Autophagy Deficiency Reprograms Cancer Metabolism Via TGFβ Signaling to drive Mesenchymal Tumor Growth

The role of chaperone-mediated autophagy (CMA) in cancer initiation and progression is not well understood due to the lack of a loss-of-function cancer models of LAMP2A, the key regulator of this process. Here, by generating an isoform-specific knockout of LAMP2A, we show that CMA deficiency promotes proliferation and tumor growth in human cancers of mesenchymal origin. Accordingly, we observed that LAMP2A diminishes in metastatic lesions compared to matched primary human tumors from the same patients. Loss of CMA enhanced TGF{beta} signaling in tumors, rewired the tumor metabolome to promote anabolic pathways and mitochondrial metabolism, meeting the metabolic requirements of rapid growth. Mechanistically, we show that TGF{beta}R2 enhances the enzymatic activity of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP), to promote the generation of nucleotides. Consequently, pharmacological inhibition of TGF{beta}-signaling in LAMP2A-KO cells suppresses G6PD activity, mitochondrial metabolism, and proliferation to WT levels. Conversely, pharmacological inhibition of mitochondrial metabolism suppressed LAMP2A-KO driven proliferation. Overall, our study provides a molecular mechanism on the CMAs tumor-suppressive function by connecting two important oncogenic pathways, the TGF{beta} signaling and PPP metabolism, to the loss-of-function LAMP2A in mesenchymal cancer types.

cancer biology↗

bioRxiv2022

Probabilistic Tracking U-fiber on the Superficial White Matter Surface

The short association fibers or U-fibers connect two neighboring gyri and travel in the superficial white matter (SWM) beneath the cortical layer. These U-fibers are essential for the understanding of neurodevelopment and neurodegeneration. However, the complex structures and the high curvature of the U-fibers lead to erroneous streamlines reconstruction of the traditional tractography since the volume-based tractography cannot use the biological characteristic of U-fibers that they tightly beneath the cortical layer. In this work, we proposed a surface-based framework for probabilistic tracking of the U-fibers on the triangular mesh of the SWM. We develop a novel approach to project the fiber orientation distributions (FODs) data onto the tangent space of the SWM surface. With the projected FODs, an advanced probabilistic tracking technique, which regularizes the streamlines based on the intrinsic geometry of the surface, is developed to reconstruct the highly bent U-fibers on the SWM surface. In the experiment, we demonstrate our method based on the high-resolution diffusion imaging data from the Human Connectome Project (HCP). We quantitatively compare the proposed method with state-of-the-art volume-based tractography from MRTrix and another surface-based tractography on the U-fibers of the central sulcus. Moreover, we show the reconstructed U-fibers on the parietal lobe and frontal lobe. The results show that our method outperforms the other two methods and successfully reconstructs the U-fibers on the cortical regions with high intersubject variability.

neuroscience↗

bioRxiv2021

Fast and specific enrichment of cancer-related exosomes by DNA-nanoweight-assisted centrifugation

Exosomes are nanoscale membrane vesicles actively released by cells and play an important role in the diagnosis of cancer-related diseases. However, it is challenging to efficiently enrich exosomes from extracellular fluids. In this work, we used DNA-tetrahedron as a nanoweight during centrifugation to precisely enrich tumor exosomes from a complex biological environment. Two different DNA tetrahedral nanostructures (DTAs), each carrying a specific aptamer for exosome biomarker recognition, were incubated with clinical samples simultaneously. One DTA triggered the cross-linking of multiple target exosomes, and therefore enabled low-speed and fast centrifugation for enrichment. The other DTA further narrowed down the target exosome subtype and initiated a hybridization chain reaction (HCR) for sensitive signal amplification. The method enabled the detection of 180 MCF-7-derived exosomes per microliter and 560 HepG2-derived exosomes per microliter, with 1000-fold higher sensitivity than conventional ELISA. This easy-to-operate method can enrich exosomes with excellent specificity and therefore will be appealing in biomedical research and clinical diagnosis.

biochemistry↗