Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

Authors: Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, Michelle L Varney, Hesham Hassan, Jixin Dong, Liying Geng, Jing Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh K Singh, Shi-Jian Ding

Published in: BMC Cancer | Issue 1/2014

Login to get access

Abstract

Background

KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

Methods

We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer.

Results

KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility.

Conclusions

Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it may represent a novel target for biomarker development and a novel therapeutic target for breast cancer.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics. CA Cancer J Clin. 2010, 60 (5): 277-300. 10.3322/caac.20073.CrossRefPubMed
2.
Karnoub AE, Weinberg RA: Chemokine networks and breast cancer metastasis. Breast Dis. 2006, 26: 75-85.CrossRefPubMed
3.
Wang Y, Ding SJ, Wang W, Jacobs JM, Qian WJ, Moore RJ, Yang F, Camp DG, Smith RD, Klemke RL: Profiling signaling polarity in chemotactic cells. Proc Natl Acad Sci USA. 2007, 104: 8328-8333. 10.1073/pnas.0701103104.CrossRefPubMedPubMedCentral
4.
Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, Clark L, Bayani N, Coppe JP, Tong F, Speed T, Spellman PT, DeVries S, Lapuk A, Wang NJ, Kuo WL, Stilwell JL, Pinkel D, Albertson DG, Waldman FM, McCormick F, Dickson RB, Johnson MD, Lippman M, Ethier S, Gazdar A, Gray JW: A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006, 10: 515-527. 10.1016/j.ccr.2006.10.008.CrossRefPubMedPubMedCentral
5.
Abe S, Usami S, Nakamura Y: Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters’ cells and the fibrocytes, as the cause of nonsyndromic hearing loss. J Hum Genet. 2003, 48: 564-570. 10.1007/s10038-003-0079-2.CrossRefPubMed
6.
Paunu N, Lahermo P, Onkamo P, Ollikainen V, Rantala I, Helen P, Simola KO, Kere J, Haapasalo H: A novel low-penetrance locus for familial glioma at 15q23-q26.3. Cancer Res. 2002, 62: 3798-3802.PubMed
7.
Kao J, Salari K, Bocanegra M, Choi YL, Girard L, Gandhi J, Kwei KA, Hernandez-Boussard T, Wang P, Gazdar AF, Minna JD, Pollack JR: Molecular profiling of breast cancer cell lines defines relevant tumor models and provides a resource for cancer gene discovery. PLoS One. 2009, 4: e6146-10.1371/journal.pone.0006146.CrossRefPubMedPubMedCentral
8.
Matsuzaki S, Tanaka F, Mimori K, Tahara K, Inoue H, Mori M: Clinicopathologic significance of KIAA1199 overexpression in human gastric cancer. Ann Surg Oncol. 2009, 16: 2042-2051. 10.1245/s10434-009-0469-6.CrossRefPubMed
9.
Birkenkamp-Demtroder K, Maghnouj A, Mansilla F, Thorsen K, Andersen CL, Oster B, Hahn S, Orntoft TF: Repression of KIAA1199 attenuates Wnt-signalling and decreases the proliferation of colon cancer cells. Br J Cancer. 2011, 105: 552-561. 10.1038/bjc.2011.268.CrossRefPubMedPubMedCentral
10.
Michishita E, Garces G, Barrett JC, Horikawa I: Upregulation of the KIAA1199 gene is associated with cellular mortality. Cancer Lett. 2006, 239: 71-77. 10.1016/j.canlet.2005.07.028.CrossRefPubMed
11.
Kostic C, Shaw PH: Isolation and characterization of sixteen novel p53 response genes. Oncogene. 2000, 19: 3978-3987. 10.1038/sj.onc.1203747.CrossRefPubMed
12.
Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC: From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics. 2004, 3: 73-81.CrossRefPubMed
13.
Jami M-S, Barreiro C, García-Estrada C, Martín J-F: Proteome analysis of the penicillin producer Penicillium chrysogenum: characterization of protein changes during the industrial strain improvement. Mol Cell Proteomics MCP. 2010, 9: 1182-1198. 10.1074/mcp.M900327-MCP200.CrossRefPubMed
14.
Hou J, Dong J, Sun L, Geng L, Wang J, Zheng J, Li Y, Bridge J, Hinrichs SH, Ding SJ: Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274. J Transl Med. 2011, 9: 64-10.1186/1479-5876-9-64.CrossRefPubMedPubMedCentral
15.
Varney ML, Johansson SL, Singh RK: Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am J Clin Pathol. 2006, 125: 209-216. 10.1309/VPL5-R3JR-7F1D-6V03.CrossRefPubMed
16.
Huang X, Tolmachev AV, Shen Y, Liu M, Huang L, Zhang Z, Anderson GA, Smith RD, Chan WC, Hinrichs SH, Fu K, Ding SJ: UNiquant, a program for quantitative proteomics analysis using stable isotope labeling. J Proteome Res. 2011, 10: 1228-1237. 10.1021/pr1010058.CrossRefPubMedPubMedCentral
17.
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995, 57: 289-300.
18.
Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS: Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009, 27: 1160-1167. 10.1200/JCO.2008.18.1370.CrossRefPubMedPubMedCentral
19.
Gluck S, Ross JS, Royce M, Jr ME F, Perou CM, Avisar E, Wu L: TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine +/− trastuzumab. Breast Cancer Res Treat. 2011, 132 (3): 781-791. 2011/03/05CrossRefPubMed
20.
Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S: X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 2006, 9: 121-132. 10.1016/j.ccr.2006.01.013.CrossRefPubMed
21.
22.
Oltvai ZN, Milliman CL, Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993, 74: 609-619. 10.1016/0092-8674(93)90509-O.CrossRefPubMed
23.
Schmitt E, Paquet C, Beauchemin M, Dever-Bertrand J, Bertrand R: Characterization of Bax-sigma, a cell death-inducing isoform of Bax. Biochem Biophys Res Commun. 2000, 270: 868-879. 10.1006/bbrc.2000.2537.CrossRefPubMed
24.
Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ: A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. Embo J. 1995, 14: 5589-5596.PubMedPubMedCentral
25.
Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM: FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 1995, 81: 505-512. 10.1016/0092-8674(95)90071-3.CrossRefPubMed
26.
Garcia-Domingo D, Leonardo E, Grandien A, Martinez P, Albar JP, Izpisua-Belmonte JC, Martinez AC: DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development. Proc Natl Acad Sci USA. 1999, 96: 7992-7997. 10.1073/pnas.96.14.7992.CrossRefPubMedPubMedCentral
27.
Kamada S, Kikkawa U, Tsujimoto Y, Hunter T: A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association. Mol Cell Biol. 2005, 25: 9469-9477. 10.1128/MCB.25.21.9469-9477.2005.CrossRefPubMedPubMedCentral
28.
Peluso JJ, Romak J, Liu X: Progesterone receptor membrane component-1 (PGRMC1) is the mediator of progesterone’s antiapoptotic action in spontaneously immortalized granulosa cells as revealed by PGRMC1 small interfering ribonucleic acid treatment and functional analysis of PGRMC1 m. Endocrinology. 2008, 149: 534-543. 10.1210/en.2007-1050.CrossRefPubMed
29.
Crudden G, Loesel R, Craven RJ: Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human progesterone receptor) in tumors. Tumour Biol. 2005, 26: 142-146. 10.1159/000086485.CrossRefPubMed
30.
Tai YT, Lee S, Niloff E, Weisman C, Strobel T, Cannistra SA: BAX protein expression and clinical outcome in epithelial ovarian cancer. J Clin Oncol. 1998, 16: 2583-2590.PubMed
31.
He H, Li J, Weng S, Li M, Yu Y: S100A11: diverse function and pathology corresponding to different target proteins. Cell Biochem Biophys. 2009, 55: 117-126. 10.1007/s12013-009-9061-8.CrossRefPubMed
32.
Still IH, Vince P, Cowell JK: The third member of the transforming acidic coiled coil-containing gene family, TACC3, maps in 4p16, close to translocation breakpoints in multiple myeloma, and is upregulated in various cancer cell lines. Genomics. 1999, 58: 165-170. 10.1006/geno.1999.5829.CrossRefPubMed
33.
Schneider L, Essmann F, Kletke A, Rio P, Hanenberg H, Schulze-Osthoff K, Nurnberg B, Piekorz RP: TACC3 depletion sensitizes to paclitaxel-induced cell death and overrides p21WAF-mediated cell cycle arrest. Oncogene. 2008, 27: 116-125. 10.1038/sj.onc.1210628.CrossRefPubMed
34.
Takenawa T, Suetsugu S: The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. 2007, 8: 37-48. 10.1038/nrm2069.CrossRefPubMed
35.
Sagara M, Kawasaki Y, Iemura SI, Natsume T, Takai Y, Akiyama T: Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration. Oncogene. 2009, 28: 1357-1365. 10.1038/onc.2008.478.CrossRefPubMed
36.
Egging D, van den Berkmortel F, Taylor G, Bristow J, Schalkwijk J: Interactions of human tenascin-X domains with dermal extracellular matrix molecules. Arch Dermatol Res. 2007, 298: 389-396.CrossRefPubMed
37.
Hughes L, Malone C, Chumsri S, Burger AM, McDonnell S: Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity. Clin Exp Metastasis. 2008, 25: 549-557. 10.1007/s10585-008-9169-z.CrossRefPubMed
38.
Jin L, Williamson A, Banerjee S, Philipp I, Rape M: Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell. 2008, 133: 653-665. 10.1016/j.cell.2008.04.012.CrossRefPubMedPubMedCentral
39.
Lee JH, You J, Dobrota E, Skalnik DG: Identification and characterization of a novel human PP1 phosphatase complex. J Biol Chem. 2010, 285: 24466-24476. 10.1074/jbc.M110.109801.CrossRefPubMedPubMedCentral
40.
Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H: PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006, 10: 575-585. 10.1016/j.devcel.2006.03.010.CrossRefPubMed
41.
Warburg O: On the origin of cancer cells. Science (80-). 1956, 123: 309-314. 10.1126/science.123.3191.309.CrossRef
42.
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB: The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7: 11-20. 10.1016/j.cmet.2007.10.002.CrossRefPubMed
Metadata
Title
Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness
Authors
Mohammad-Saeid Jami
Jinxuan Hou
Miao Liu
Michelle L Varney
Hesham Hassan
Jixin Dong
Liying Geng
Jing Wang
Fang Yu
Xin Huang
Hong Peng
Kai Fu
Yan Li
Rakesh K Singh
Shi-Jian Ding
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-194

Other articles of this Issue 1/2014

BMC Cancer 1/2014 Go to the issue

Research article

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species

Research article

Trastuzumab in advanced breast cancer – a decade of experience in Germany

Research article

A genomics approach to identify susceptibilities of breast cancer cells to “fever-range” hyperthermia

Research article

Cancer suspicion in general practice, urgent referral and time to diagnosis: a population-based GP survey and registry study

Research article

Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis

Study protocol

Improving sexual health in men with prostate cancer: randomised controlled trial of exercise and psychosexual therapies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits