Blocking the cleavage of filamin A by calpain inhibitor decreases tumor cell growth

Salimi, RezaGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)

Filamin A (FLNA) is the most abundant and widely expressed isoform of filamin in human tissues. It is cleaved by calpain at the hinge 1 and 2 domains, producing a 90-kDa carboxyl-terminal fragment (FLNACT). Recently, it has been shown that FLNACTmediates cell signaling and transports transcription factors into the cell nucleus. However, the significance of cleavage of FLNA by calpain has not been studied in cancer cell growth. Calpeptin is a chemical inhibitor of both calpain 1 and 2 that cleaves FLNA. In this study, we questioned if inhibiting calpain using calpeptin would decrease tumor cell proliferation, migration, invasion, and colony formation.Human melanoma (A7), prostate cancer (PC3), mouse fibrosarcoma (T241) and endothelial (MS1) cells were assayed for proliferation, migration, invasion and colony formation after treatment with calpeptin. Cell lysates were immunoblotted for FLNA and FLNACTResults: Calpeptin treatment of these cells resulted in a decreased production of FLNACTCalpeptin-treated human and mouse tumor cells displayed impaired proliferation, migration, and colony formation.These data suggest that the cleavage of FLNA by calpain is an important cellular event in the regulation of tumor cell growth.

Bandaru, SashidarGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xbands (author)
Devarakonda, SravaniGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xdevsr (author)
Gökalp, SevtapGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)
Ala, ChanduGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)
Alvandian, Ali (author)
Yener, Nilgün (author)
Akyürek, Levent,1966Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xakyle (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)

In:Anticancer Research: Anticancer Research USA Inc.38:4, s. 2079-20850250-70051791-7530

By the author/editor: Salimi, Reza; Bandaru, Sashida ...; Devarakonda, Sra ...; Gökalp, Sevtap; Ala, Chandu; Alvandian, Ali; show more...; Yener, Nilgün; Akyürek, Levent, ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Medical Biotechn ...; and Medical Biotechn ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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