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Ovarian cancer-associated antigen 66 (OVA66), also known as CML66 (GenBank Accession No. AF283301) was first identified
in an ovarian carcinoma cDNA expression library and was shown to play a role in tumorigenesis. Here, we find that OVA66
influences tumorigenesis by regulating the type I insulin-like growth factor receptor (IGF-1R) signaling pathway. Stable knockdown of
OVA66 in cancer cells attenuated phosphorylation of IGF-1R and ERK1/2-Hsp27; similarly, a higher level of p-IGF-1R and ERK1/2-
Hsp27 signaling were also detected after OVA66 overexpression in HO8910 cells. In vivo knockdown of OVA66 both reduced tumor
burden in nude mice and decreased phosphorylation of IGF-1R, ERK1/2, and hsp27. We blocked IGF-1R function both by siRNA
and with the chemical inhibitor linsitinib (OSI-906). By either method, tumorigenesis was inhibited regardless of OVA66 expression;
thus, mechanistically, IGF-1R likely lies downstream of OVA66 in cancer cells. We also found that OVA66 regulates expression of
MDM2; this attenuates ubiquitination of IGF-1R in response to IGF-1 stimulation and promotes active ERK1/2 signaling. Thus, we
propose that combined overexpression of OVA66 and MDM2 promotes oncogenesis by enhancing activation of the IGF-1R-ERK1/2
1. Wang H, Wang Y, Qian L, Wang X, Gu H, Dong X, Huang S, Jin M, Ge H, Xu C, Zhang Y (2016) RNF216 contributes to
proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy. Oncotarget May 18
2. Song FF, Xia LL, Ji P1, Tang YB, Huang ZM, Zhu L, Zhang J, Wang JQ, Zhao GP, Ge HL, Zhang Y, Wang Y (2015) Human
dCTP pyrophosphatase 1 promotes breast cancer cell growth and stemness through the modulation on 5-methyl-dCTP
metabolism and global hypomethylation. Oncogenesis Jun 15: 4:e159.
3. Zhang R, Jin S, Rao W, Song F, Yin Q, Wang Y, Wang L, Xi Y, Zhang X, Wang M, Ge H. OVA12 (2015) a novel tumor
antigen, promotes cancer cell growth and inhibits 5-fluorouracil-induced apoptosis. Cancer Lett Feb 1:357(1):141-51.
4. Rao W, Xie G, Zhang Y, Wang S, Wang Y, Zhang H, Song F, Zhang R, Yin Q, Shen L, Ge H (2014) OVA66, a tumor
associated protein, induces oncogenic transformation of NIH3T3 cells. PLoS One. Mar 14;9(3): e85705.
5. Zhang Y, Ye WY, Wang JQ, Wang SJ, Ji P, Zhou GY, Zhao GP, Ge HL, Wang Y (2013) dCTP pyrophosphohydrase exhibits
nucleic accumulation in multiple carcinomas. Eur J Histochem Sep 25:57(3):e29.
Hailiang Ge, male, is professor of Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine. He graduated from Shanghai Second Medical University in 1977 majoring in medicine. Then he obtained the Master Degree in Nuclear Medicine of Ruijin Hospital, Shanghai Second Medical University in 1985 and got the Doctor Degree in Immunology of Shanghai Second Medical University in 1991. He worked on research as a postdoctoral fellow in the Department of Microbiology and Immunology, University of California, San Francisco, U.S.A. from 1992 to 1995. In 1998 and 2002, he studied in School of Medicine, University of Michigan and School of Medicine, University of Pittsburgh, U.S.A. as a visiting professor respectively.