Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach
Abstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-08904-8 |
| _version_ | 1811335699578748928 |
|---|---|
| author | Tomohiro Soda Yasuyuki Gen Kei Terasaki Naoto Iwai Tomoko Kitaichi Osamu Dohi Hiroyoshi Taketani Yuya Seko Atsushi Umemura Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Hideyuki Konishi Yuji Naito Yoshito Itoh Kohichiroh Yasui |
| author_facet | Tomohiro Soda Yasuyuki Gen Kei Terasaki Naoto Iwai Tomoko Kitaichi Osamu Dohi Hiroyoshi Taketani Yuya Seko Atsushi Umemura Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Hideyuki Konishi Yuji Naito Yoshito Itoh Kohichiroh Yasui |
| author_sort | Tomohiro Soda |
| collection | DOAJ |
| description | Abstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach. |
| first_indexed | 2024-04-13T17:29:04Z |
| format | Article |
| id | doaj.art-bec98801d67c4a62b99b65ef2b2789ea |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T17:29:04Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bec98801d67c4a62b99b65ef2b2789ea2022-12-22T02:37:40ZengNature PortfolioScientific Reports2045-23222022-03-0112111210.1038/s41598-022-08904-8Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomachTomohiro Soda0Yasuyuki Gen1Kei Terasaki2Naoto Iwai3Tomoko Kitaichi4Osamu Dohi5Hiroyoshi Taketani6Yuya Seko7Atsushi Umemura8Taichiro Nishikawa9Kanji Yamaguchi10Michihisa Moriguchi11Hideyuki Konishi12Yuji Naito13Yoshito Itoh14Kohichiroh Yasui15Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of MedicineSchool of Health Sciences, Bukkyo UniversityAbstract Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell–cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell–cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach.https://doi.org/10.1038/s41598-022-08904-8 |
| spellingShingle | Tomohiro Soda Yasuyuki Gen Kei Terasaki Naoto Iwai Tomoko Kitaichi Osamu Dohi Hiroyoshi Taketani Yuya Seko Atsushi Umemura Taichiro Nishikawa Kanji Yamaguchi Michihisa Moriguchi Hideyuki Konishi Yuji Naito Yoshito Itoh Kohichiroh Yasui Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach Scientific Reports |
| title | Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| title_full | Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| title_fullStr | Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| title_full_unstemmed | Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| title_short | Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| title_sort | loss of kap3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach |
| url | https://doi.org/10.1038/s41598-022-08904-8 |
| work_keys_str_mv | AT tomohirosoda lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT yasuyukigen lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT keiterasaki lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT naotoiwai lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT tomokokitaichi lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT osamudohi lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT hiroyoshitaketani lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT yuyaseko lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT atsushiumemura lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT taichironishikawa lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT kanjiyamaguchi lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT michihisamoriguchi lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT hideyukikonishi lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT yujinaito lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT yoshitoitoh lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach AT kohichirohyasui lossofkap3decreasesintercellularadhesionandimpairsintracellulartransportoflaminininsignetringcellcarcinomaofthestomach |