Silencing of type Iγ phosphatidylinositol phosphate kinase suppresses ovarian cancer cell proliferation, migration and invasion
Authors: Kun Ling
Xiaofeng Yang
Yan Huang
Junli Xue
Chunhua Chen
Siyu Cao
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Metastasis; Ovarian cancer; PIPKIγ; Cell migration; Invasion
Affiliations: Department of Gynecology and Obstetrics, The First Affiliated Hospital of the Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55901, USA., Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.

Abstract:  Metastasis is the major cause of death in ovarian cancer patients. Given that the molecular mechanism underlying metastasis formation is critical for improving therapeutic development and clinical treatment, it must be fully understood. Recent studies have revealed that lipid kinase type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the metastasis of breast cancer and colon cancer by regulating cell migration and invasion. However, its role in the progression of ovarian cancer is unclear. Here we showed that PIPKIγ expression is upregulated in multiple epithelial ovarian cancer cell lines. Silencing of PIPKIγ impaired PI3K/AKT signaling and inhibited the aggressive behaviors of epithelial ovarian cancer cells, including proliferation, migration and invasion. Moreover, we found that PIPKIγ was required for the activation of signal transducer and activator of transcription 3 (STAT3) in epithelial ovarian cancer cells, indicating that STAT3 may also be engaged in the PIPKIγ-dependent aggressiveness of epithelial ovarian cancer cells. Our results, for the first time, identified PIPKIγ as a novel regulator in epithelial ovarian cancer cells that promotes cell proliferation, migration and invasion by activating multiple signaling pathways. Therefore, we propose that PIPKIγ could potentially be a therapeutic target for the early detection and treatment of epithelial ovarian cancer. Further studies employing in vivo models are necessary to test this possibility. 

Retracted: No

PubPeer comments:
 From a wechat blog, the Figure 3A has duplicated area. ![file] ![file] , 
 Update: Apologies, but the image is not showing up correctly. I tried uploading it several times, made a new version, etc. but it keeps on giving me troubles. Will try to resolve. For now, use this Imgur link: https: imgur.com CotVePN Figure 3. * Red boxes: Two panels appear to show an overlap. ![file] , 
 Dear Dr. Bik, Thank you very much for bringing this issue to our attention. This paper was a collaborative project between us and Dr. Xiaofeng Yang s group at Xi an Jiaotong Univeristy. The first author Dr. Siyu Cao, who is affiliated with Xi an Jiaotong University, returned to China couple of years ago. Dr. Cao is under quarantine right now because of COVID-19 and I have provided her contact information to you via Pubpeer Contact. After communicating with Dr. Cao and carefully checking her lab notebooks, we realized that she unintentionally mixed up the original pictures when she prepared the representative image for the middle panel of Fig. 3B, where cells were treated with one of the two PIPKIgamma-specific siRNAs (PIPKIy-1). However, the data presented in Fig. 3D were quantification by counting cell numbers in original images from three independent experiments, each including 5 randomly selected microscope fields. The mix-up of the representative image for PIPKIy-1 in Fig. 3B does not affect the conclusion of this experiment. We have contacted *Oncology Reports* to make the correction. According to Mayo Clinic policy, all microscope images Dr. Cao saved in the lab computer (Mayo Clinic property) have been archived and locked up after her position at Mayo Clinic was terminated. We are working with our IT department to unlock the hard drive and extract the original images. As one of the co-corresponding authors of this paper, I sincerely apologize for this inadvertent error and possible confusion it caused. I truly appreciate your helping us catch it. Sincerely, Kun Ling , 
 Corrigendum [18 February 2021] . ---------------------  Subsequently to the publication of the above paper, the authors have drawn to our attention that the middle panel in Fig. 3B, representing the migration of PIPKIu03b3-depleted cells (PIPKIu03b3-1), was inadvertently mixed up with the left panel of control cells (siRNA Ctrl). The results presented in Fig. 3D, however, were quantified based on the original images from three independent experiments, each containing five randomly picked microscopic fields.  The authors were able to re-examine the original data files and retrieve the correct data panels. The revised version of Fig. 3, featuring the correct data for the u2018PIPKIu03b3-1u2019 panel in Fig. 3B, is shown below. Note that the error made inadvertently with the selection of the representative image for PIPKIu03b3-1 in Fig. 3B did not affect the overall conclusions reported for this experiment. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. ![] Figure 3. - Loss of PIPKIu03b3 suppresses the migration of epithelial ovarian cancer cells. Migration assay was performed using modified Boyden chambers in triplicates using OVCAR-8 (A) or SKOV-3 (B) cells transfected with the indicated siRNAs (control, PIPKIu03b3-1 and PIPKIu03b3-2). (A and B) Cells migrating across the membrane were fixed and stained, then imaged under a microscope. (C and D) Cells imaged in A and B were counted in five random fields under u00d720 magnification and averaged, and then statistically analyzed from three independent experiments and plotted. (D) Rescue experiments were conducted using SKOV-3 cells by introducing the expression of siRNA-resistant PIPKIu03b3 isoform 1 and 2 by transient transfection, followed by transfection of control or PIPKIu03b3-specific siRNAs. Then cells were subjected to migration assay and quantified as described above. Data are presented mean u00b1 SD. **P 0.01. PIPKIu03b3, type Iu03b3 phosphatidylinositol phosphate kinase. ,