Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach.

Soda T
 Gen Y
 Terasaki K
 Iwai N
 Kitaichi T
 Dohi O
 Taketani H
 Seko Y
 Umemura A
 Nishikawa T
 Yamaguchi K
 Moriguchi M
 Konishi H
 Naito Y
 Itoh Y
 Yasui K.

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.

Scientific Reports

Springer Nature

12

10.1038/s41598-022-08904-8.

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