Role of km23-1 in RhoA/actin-based cell migration.
km23-1 was originally identified as a TGFß receptor-interacting protein that plays an important role in TGFß signaling. Moreover, km23-1 is actually part of an ancient superfamily of NTPase-regulatory proteins, widely represented in archaea and bacteria. To further elucidate the function of km23-1, we identified novel protein interacting partners for km23-1 by using tandem affinity purification (TAP) and tandem mass spectrometry (MS). Here we show that km23-1 interacted with a class of proteins involved in actin-based cell motility and modulation of the actin cytoskeleton. We further showed that km23-1 modulates the formation of a highly organized stress fiber network. More significantly, we demonstrated that knockdown (KD) of km23-1 decreased RhoA activation in Mv1Lu epithelial cells. Finally, our results demonstrated for the first time that depletion of km23-1 inhibited cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays. Overall, our findings demonstrate that km23-1 regulates RhoA and motility-associated actin modulating proteins, suggesting that km23-1 may represent a novel target for anti-metastatic therapy.
Department of Biochemistry and Molecular Biology, Penn State Hershey College of Medicine, PA 17033, USA.
Qunyan
Q
Jin
Nageswara R
NR
Pulipati
Weidong
W
Zhou
Cory M
CM
Staub
Lance A
LA
Liotta
Kathleen M
KM
Mulder
D000199:Actins / Q000096:biosynthesis*; D002465:Cell Movement; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000502:physiology*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology*; D014945:Wound Healing; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis*
D000199:Actins; C504797:DYNLRB1 protein, human; C066737:RHOA protein, human; D056445:Cytoplasmic Dyneins; D020742:rhoA GTP-Binding Protein