FMNL1 promotes proliferation and migration of leukemia cells

Patricia Favaro; Fabiola Traina; João Agostinho Machado-Neto; Mariana Lazarini; Matheus Rodrigues Lopes; João Kleber Novais Pereira; Fernando Ferreira Costa; Elvira Infante; Anne J Ridley; Sara Teresinha Olalla Saad

doi:10.1189/jlb.0113057

FMNL1 promotes proliferation and migration of leukemia cells

Patricia Favaro, Fabiola Traina, João Agostinho Machado-Neto, Mariana Lazarini, Matheus Rodrigues Lopes, João Kleber Novais Pereira, Fernando Ferreira Costa, Elvira Infante, Anne J Ridley, Sara Teresinha Olalla Saad

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

Abstract

The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.

Original language	English
Pages (from-to)	503-512
Number of pages	10
Journal	Journal of Leukocyte Biology
Volume	94
Issue number	3
DOIs	https://doi.org/10.1189/jlb.0113057
Publication status	Published - Sept 2013

Keywords

Animals
Apoptosis
Cell Movement
Cell Proliferation
Cells, Cultured
Cytoskeletal Proteins
Humans
Leukemia
Mice
RNA, Small Interfering
rac1 GTP-Binding Protein

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10.1189/jlb.0113057

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title = "FMNL1 promotes proliferation and migration of leukemia cells",

abstract = "The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.",

keywords = "Animals, Apoptosis, Cell Movement, Cell Proliferation, Cells, Cultured, Cytoskeletal Proteins, Humans, Leukemia, Mice, RNA, Small Interfering, rac1 GTP-Binding Protein",

author = "Patricia Favaro and Fabiola Traina and Machado-Neto, {Jo{\~a}o Agostinho} and Mariana Lazarini and Lopes, {Matheus Rodrigues} and Pereira, {Jo{\~a}o Kleber Novais} and Costa, {Fernando Ferreira} and Elvira Infante and Ridley, {Anne J} and Saad, {Sara Teresinha Olalla}",

year = "2013",

month = sep,

doi = "10.1189/jlb.0113057",

language = "English",

volume = "94",

pages = "503--512",

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issn = "0741-5400",

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T1 - FMNL1 promotes proliferation and migration of leukemia cells

AU - Favaro, Patricia

AU - Traina, Fabiola

AU - Machado-Neto, João Agostinho

AU - Lazarini, Mariana

AU - Lopes, Matheus Rodrigues

AU - Pereira, João Kleber Novais

AU - Costa, Fernando Ferreira

AU - Infante, Elvira

AU - Ridley, Anne J

AU - Saad, Sara Teresinha Olalla

PY - 2013/9

Y1 - 2013/9

N2 - The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.

AB - The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.

KW - Animals

KW - Apoptosis

KW - Cell Movement

KW - Cell Proliferation

KW - Cells, Cultured

KW - Cytoskeletal Proteins

KW - Humans

KW - Leukemia

KW - Mice

KW - RNA, Small Interfering

KW - rac1 GTP-Binding Protein

U2 - 10.1189/jlb.0113057

DO - 10.1189/jlb.0113057

M3 - Article

C2 - 23801653

SN - 0741-5400

VL - 94

SP - 503

EP - 512

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

IS - 3

ER -

FMNL1 promotes proliferation and migration of leukemia cells

Abstract

Keywords

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