The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma

Pei Fang Hung, Tse-Ming Hong, Yi Chiung Hsu, Hsuan Yu Chen, Yih Leong Chang, Chen Tu Wu, Gee Chen Chang, Yuh Shan Jou, Szu Hua Pan, Pan Chyr Yang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

Original languageEnglish
Article numbere61664
JournalPloS one
Volume8
Issue number4
DOIs
Publication statusPublished - 2013 Apr 23

Fingerprint

adenocarcinoma
metastasis
Tumors
lungs
Neoplasm Metastasis
neoplasms
Growth
Adhesion
adhesion
Neoplasms
Proteins
proteins
cadherins
CD146 Antigens
Kinesin
Molecules
Extracellular Matrix Proteins
comparative genomic hybridization
Laminin
kinesin

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hung, P. F., Hong, T-M., Hsu, Y. C., Chen, H. Y., Chang, Y. L., Wu, C. T., ... Yang, P. C. (2013). The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma. PloS one, 8(4), [e61664]. https://doi.org/10.1371/journal.pone.0061664
Hung, Pei Fang ; Hong, Tse-Ming ; Hsu, Yi Chiung ; Chen, Hsuan Yu ; Chang, Yih Leong ; Wu, Chen Tu ; Chang, Gee Chen ; Jou, Yuh Shan ; Pan, Szu Hua ; Yang, Pan Chyr. / The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma. In: PloS one. 2013 ; Vol. 8, No. 4.
@article{6a7c7ccec911442dba8a1d85c2f4fcce,
title = "The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma",
abstract = "The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30{\%} loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30{\%} of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.",
author = "Hung, {Pei Fang} and Tse-Ming Hong and Hsu, {Yi Chiung} and Chen, {Hsuan Yu} and Chang, {Yih Leong} and Wu, {Chen Tu} and Chang, {Gee Chen} and Jou, {Yuh Shan} and Pan, {Szu Hua} and Yang, {Pan Chyr}",
year = "2013",
month = "4",
day = "23",
doi = "10.1371/journal.pone.0061664",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

Hung, PF, Hong, T-M, Hsu, YC, Chen, HY, Chang, YL, Wu, CT, Chang, GC, Jou, YS, Pan, SH & Yang, PC 2013, 'The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma', PloS one, vol. 8, no. 4, e61664. https://doi.org/10.1371/journal.pone.0061664

The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma. / Hung, Pei Fang; Hong, Tse-Ming; Hsu, Yi Chiung; Chen, Hsuan Yu; Chang, Yih Leong; Wu, Chen Tu; Chang, Gee Chen; Jou, Yuh Shan; Pan, Szu Hua; Yang, Pan Chyr.

In: PloS one, Vol. 8, No. 4, e61664, 23.04.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Motor Protein KIF14 Inhibits Tumor Growth and Cancer Metastasis in Lung Adenocarcinoma

AU - Hung, Pei Fang

AU - Hong, Tse-Ming

AU - Hsu, Yi Chiung

AU - Chen, Hsuan Yu

AU - Chang, Yih Leong

AU - Wu, Chen Tu

AU - Chang, Gee Chen

AU - Jou, Yuh Shan

AU - Pan, Szu Hua

AU - Yang, Pan Chyr

PY - 2013/4/23

Y1 - 2013/4/23

N2 - The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

AB - The motor protein kinesin superfamily proteins (KIFs) are involved in cancer progression. The depletion of one of the KIFs, KIF14, might delay the metaphase-to-anaphase transition, resulting in a binucleated status, which enhances tumor progression; however, the exact correlation between KIF14 and cancer progression remains ambiguous. In this study, using loss of heterozygosity and array comparative genomic hybridization analyses, we observed a 30% loss in the regions surrounding KIF14 on chromosome 1q in lung adenocarcinomas. In addition, the protein expression levels of KIF14 in 122 lung adenocarcinomas also indicated that approximately 30% of adenocarcinomas showed KIF14 down-regulation compared with the expression in the bronchial epithelial cells of adjacent normal counterparts. In addition, the reduced expression of KIF14 mRNA or proteins was correlated with poor overall survival (P = 0.0158 and <0.0001, respectively), and the protein levels were also inversely correlated with metastasis (P<0.0001). The overexpression of KIF14 in lung adenocarcinoma cells inhibited anchorage-independent growth in vitro and xenograft tumor growth in vivo. The overexpression and silencing of KIF14 also inhibited or enhanced cancer cell migration, invasion and adhesion to the extracellular matrix proteins laminin and collagen IV. Furthermore, we detected the adhesion molecules cadherin 11 (CDH11) and melanoma cell adhesion molecule (MCAM) as cargo on KIF14. The overexpression and silencing of KIF14 enhanced or reduced the recruitment of CDH11 in the membrane fraction, suggesting that KIF14 might act through recruiting adhesion molecules to the cell membrane and modulating cell adhesive, migratory and invasive properties. Thus, KIF14 might inhibit tumor growth and cancer metastasis in lung adenocarcinomas.

UR - http://www.scopus.com/inward/record.url?scp=84876551334&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876551334&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0061664

DO - 10.1371/journal.pone.0061664

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e61664

ER -