TY - JOUR
T1 - LASP1, CERS6, and Actin Form a Ternary Complex That Promotes Cancer Cell Migration
AU - Niimi, Atsuko
AU - Limsirichaikul, Siripan
AU - Kano, Keiko
AU - Mizutani, Yasuyoshi
AU - Takeuchi, Toshiyuki
AU - Sawangsri, Patinya
AU - Tran, Dat Quoc
AU - Kawamoto, Yoshiyuki
AU - Suzuki, Motoshi
N1 - Funding Information:
This research was funded by a Grant-in-Aid for Scientific Research (18H02698, MS; 22K07263, AN; 21K08217, YM), a TR-SPRINT Grant (18lm0203005j0002, MS), a Novartis Research Grant (MS), and a Fujita Health University Research Grant (MS).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - CERS6 is associated with metastasis and poor prognosis in non-small cell lung cancer (NSCLC) patients through d18:1/C16:0 ceramide (C16 ceramide)-mediated cell migration, though the detailed mechanism has not been elucidated. In the present study, examinations including co-immunoprecipitation, liquid chromatography, and tandem mass spectrometry analysis were performed to identify a novel binding partner of CERS6. Among the examined candidates, LASP1 was a top-ranked binding partner, with the LIM domain possibly required for direct interaction. In accord with those findings, CERS6 and LASP1 were found to co-localize on lamellipodia in several lung cancer cell lines. Furthermore, silencing of CERS6 and/or LASP1 significantly suppressed cell migration and lamellipodia formation, whereas ectopic addition of C16 ceramide partially rescued those phenotypes. Both LASP1 and CERS6 showed co-immunoprecipitation with actin, with those interactions markedly reduced when the LASP1–CERS6 complex was abolished. Based on these findings, it is proposed that LASP1–CERS6 interaction promotes cancer cell migration.
AB - CERS6 is associated with metastasis and poor prognosis in non-small cell lung cancer (NSCLC) patients through d18:1/C16:0 ceramide (C16 ceramide)-mediated cell migration, though the detailed mechanism has not been elucidated. In the present study, examinations including co-immunoprecipitation, liquid chromatography, and tandem mass spectrometry analysis were performed to identify a novel binding partner of CERS6. Among the examined candidates, LASP1 was a top-ranked binding partner, with the LIM domain possibly required for direct interaction. In accord with those findings, CERS6 and LASP1 were found to co-localize on lamellipodia in several lung cancer cell lines. Furthermore, silencing of CERS6 and/or LASP1 significantly suppressed cell migration and lamellipodia formation, whereas ectopic addition of C16 ceramide partially rescued those phenotypes. Both LASP1 and CERS6 showed co-immunoprecipitation with actin, with those interactions markedly reduced when the LASP1–CERS6 complex was abolished. Based on these findings, it is proposed that LASP1–CERS6 interaction promotes cancer cell migration.
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U2 - 10.3390/cancers15102781
DO - 10.3390/cancers15102781
M3 - Article
AN - SCOPUS:85160690722
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 10
M1 - 2781
ER -