| Literature DB >> 36044553 |
Kohji Yamada1, Saya Motohashi1, Tsunekazu Oikawa2, Naoko Tago1, Rei Koizumi1, Masaya Ono3, Toshiaki Tachibana4, Ayano Yoshida1, Saishu Yoshida1, Masayuki Shimoda5, Masahiro Oka6, Yoshihiro Yoneda7, Kiyotsugu Yoshida1.
Abstract
Protein secretion in cancer cells defines tumor survival and progression by orchestrating the microenvironment. Studies suggest the occurrence of active secretion of cytosolic proteins in liver cancer and their involvement in tumorigenesis. Here, we investigated the identification of extended-synaptotagmin 1 (E-Syt1), an endoplasmic reticulum (ER)-bound protein, as a key mediator for cytosolic protein secretion at the ER-plasma membrane (PM) contact sites. Cytosolic proteins interacted with E-Syt1 on the ER, and then localized spatially inside SEC22B+ vesicles of liver cancer cells. Consequently, SEC22B on the vesicle tethered to the PM via Q-SNAREs (SNAP23, SNX3, and SNX4) for their secretion. Furthermore, inhibiting the interaction of protein kinase Cδ (PKCδ), a liver cancer-specific secretory cytosolic protein, with E-Syt1 by a PKCδ antibody, decreased in both PKCδ secretion and tumorigenicity. Results reveal the role of ER-PM contact sites in cytosolic protein secretion and provide a basis for ER-targeting therapy for liver cancer.Entities:
Keywords: PKCδ; SEC22B; cytosolic protein secretion; endoplasmic reticulum (ER); liver cancer
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Year: 2022 PMID： 36044553 PMCID： PMC9457520 DOI： 10.1073/pnas.2202730119
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779