TY - JOUR
T1 - Expression of myoferlin in human and murine carcinoma tumors
T2 - Role in membrane repair, cell proliferation, and tumorigenesis
AU - Leung, Cleo
AU - Yu, Carol
AU - Lin, Michelle I.
AU - Tognon, Cristina
AU - Bernatchez, Pascal
N1 - Funding Information:
Supported by grants from the Canadian Institutes for Health Research (CIHR), the Michael Smith Foundation for Health Research (MSFHR), the Canadian Foundation for Innovation , the British Columbia Knowledge Development Fund , the Heart and Stroke Foundation of British Columbia & Yukon , the Heart and Stroke Foundation of Canada , and the British Columbia Proteomics Network (C.L.). C.Y. and P.B. are supported by salary awards from CIHR and MSFHR ; C.T. is supported by a ReThink Breast Cancer Career Development Award .
PY - 2013/5
Y1 - 2013/5
N2 - Cancer cells are often characterized by high proliferation rates, a consequence of increased mitotic signaling coupled with unchecked cellular growth. We recently demonstrated that vascular endothelial cells unexpectedly express ferlins, a family of muscle-specific proteins capable of regulating the fusion of lipid patches to the plasma membrane, and that these highly regulated membrane fusion events are essential to endothelial cell proliferation and homeostasis. Here, we show that human and mouse breast cancer cell lines also express myoferlin at various levels, and that the processes of transformation, epithelial-mesenchymal transition, and metastasis do not appear to have any effect on myoferlin expression in vitro. In vivo, we observed that solid mouse and human carcinoma tissues also express high levels of myoferlin protein. Loss-of-function studies performed in mice revealed that myoferlin gene knockdown can attenuate cancer cell proliferation in vitro and decrease tumor burden, and that accelerated tumor cell growth appears to rely on intact myoferlin-dependent membrane repair and signaling under exponential growth conditions. To our knowledge, these data provide the first evidence of myoferlin expression in solid human and mouse tumors. We have thus identified a novel membrane repair process that likely helps sustain the high growth rates characteristic of tumors, and we suggest that interfering with normal myoferlin expression and/or membrane repair and remodeling may provide therapeutically relevant antiproliferative effects.
AB - Cancer cells are often characterized by high proliferation rates, a consequence of increased mitotic signaling coupled with unchecked cellular growth. We recently demonstrated that vascular endothelial cells unexpectedly express ferlins, a family of muscle-specific proteins capable of regulating the fusion of lipid patches to the plasma membrane, and that these highly regulated membrane fusion events are essential to endothelial cell proliferation and homeostasis. Here, we show that human and mouse breast cancer cell lines also express myoferlin at various levels, and that the processes of transformation, epithelial-mesenchymal transition, and metastasis do not appear to have any effect on myoferlin expression in vitro. In vivo, we observed that solid mouse and human carcinoma tissues also express high levels of myoferlin protein. Loss-of-function studies performed in mice revealed that myoferlin gene knockdown can attenuate cancer cell proliferation in vitro and decrease tumor burden, and that accelerated tumor cell growth appears to rely on intact myoferlin-dependent membrane repair and signaling under exponential growth conditions. To our knowledge, these data provide the first evidence of myoferlin expression in solid human and mouse tumors. We have thus identified a novel membrane repair process that likely helps sustain the high growth rates characteristic of tumors, and we suggest that interfering with normal myoferlin expression and/or membrane repair and remodeling may provide therapeutically relevant antiproliferative effects.
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U2 - 10.1016/j.ajpath.2013.01.041
DO - 10.1016/j.ajpath.2013.01.041
M3 - Article
C2 - 23499551
AN - SCOPUS:84876529480
SN - 0002-9440
VL - 182
SP - 1900
EP - 1909
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -