Page 39 - Hormel Institute Annual Report 2021-22

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so we focus on how Glut1 is targeted onto the PM in TG- Fβ1-stimulated HSCs. We found that TGFβ1-stimulated Glut1 PM localization, glycolysis, and HSC activation are mediated by the SH3 domain of Src. An abstract about this work has been accepted for a poster presentation at the Liver Meeting, AASLD, 2022, Washington DC.
The role of PKCzeta in glycolysis fueling CAF activation of HSCs.
We also investigate how Glut1 is anchored onto the PM of HSCs. We found that TGFβ1 stimulation leads to the formation of a VASP/PKCζ/Glut1 protein complex that in turn anchors Glut1 at the PM to facilitate glucose transport. This work has been presented at The FASEB Liver Biology Conference in New Orleans.
The role of CMTM6 in colorectal cancer metastasis.
In this research funded by the Windfeldt Cancer Research Award, we are testing a hypothesis that CMTM6 regulates glycolysis of colorectal cancer cells thereby facilitating liver metastasis of colorectal cancer.
Recent Publications:
• Sun, L., Wang, Y., Wang, X., Navarro- Corcuera, A., Ilyas, S., Jalan-Sakrikar, N., Gan, C., Tu, X., Shi, Y., Tu, K.,
Liu, Q., Lou, Z., Dong, H., Sharpe, A. H., Shah, V. H., & Kang, N. (2022). PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-β receptor I versus II.
Cell Rep, 38(6), 110349.
• Navarro-Corcuera, A., Sehrawat,
T. S., Jalan-Sakrikar, N., Gibbons,
H. R., Pirius, N. E., Khanal, S., Hamdan, F. H., Aseem, S. O., Cao, S., Banales, J. M., Kang, N., Faubion, W. A., LaRusso, N. F., Shah, V. H., & Huebert, R. C. (2022). Long non- coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex.
J Hepatol, 76(4), 921-933.
• Qian, X., Zhang, W., Yang, H., Zhang, L., Kang, N., & Lai, J. (2021). Role
of Yes-associated Protein-1 in Gastrointestinal Cancers and Hepatocellular Carcinoma. Explor Res Hypothesis Med, 6(3), 110-117.
independent of immune suppression, (2) HSC PD-L1 promotes the conversion of HSCs into CAFs by two distinct mechanisms for TGFβ receptor II (TβRII) vs. TGFβ receptor I (TβRI), (3) the extracellular domain of PD-L1 binds to TβRII protein to protect it from lysosomal degra- dation, (4) a C-terminal motif on PD-L1 (260-RLRKGR-265) binds to TβRI mRNA to protect it from degradation by
the RNA exosome complex, and (5) targeting HSC PD-L1 selectively suppresses liver cancer in mice. These findings have been published in Cell Reports.
The role of Src in glycolysis fueling CAF activation of HSCs.
Glucose transporter 1 (Glut1) must be at the plasma membrane (PM) of HSCs to transport glucose into cells,
Lab research activities:
https://www.hi.umn.edu/research/ research-sections/tumor-microenvironment- and-metastasis/
ORCID iD: https://orcid.org/0000-0002- 4565-7976