The SIL gene is essential for mitotic entry and survival of cancer cells.
Although mitosis is a general physiologic process, cancer cells are unusually sensitive to mitotic inhibitors. Therefore, there is an interest in the identification of novel mitotic inhibitors. Here, we report the novel discovery of the SIL gene as a regulator of mitotic entry and cell survival. The SIL gene was cloned from leukemia-associated chromosomal translocation. It encodes a cytosolic protein with an unknown function and no homology to known proteins. Previously, we observed an increased expression of SIL in multiple cancers that correlated with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. Here, we show that SIL is important for the transition from the G(2) to the M phases of the cell cycle. Inducible knockdown of SIL in cancer cells in vitro delayed entrance into mitosis, decreased activation of the CDK1 (CDC2)-cyclin B complex, and induced apoptosis in a p53-independent manner. SIL is also essential for the growth of tumor explants in mice. Thus, SIL is required for mitotic entry and cancer cell survival. Because increased expression of SIL has been noted in multiple types of cancers and correlates with metastatic spread, it may be a suitable target for novel anticancer therapy.
Erez
Ayelet
A
Chaim Sheba Cancer Research Center, Institute of Hematology, Sheba Medical Center, Tel Hashomer, Israel.
Castiel
Asher
A
Trakhtenbrot
Luba
L
Perelman
Marina
M
Rosenthal
Esther
E
Goldstein
Itamar
I
Stettner
Noa
N
Harmelin
Alon
A
Eldar-Finkelman
Hagit
H
Campaner
Stefano
S
Kirsch
Ilan
I
Izraeli
Shai
S
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008938:Mitosis / Q000235:genetics*; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D014183:Transplantation, Heterologous
D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C071236:STIL protein, human