Evidence That RASSF1C Stimulation of Lung Cancer Cell Proliferation Depends on IGFBP-5 and PIWIL1 Expression Levels

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jul 10

PMID 25007054

Citations 15

Authors

Mark E Reeves

Matthew Firek

Shin-Tai Chen

Yousef G Amaar

Affiliations

Soon will be listed here.

Abstract

RASSF1C is a major isoform of the RASSF1 gene, and is emerging as an oncogene. This is in contradistinction to the RASSF1A isoform, which is an established tumor suppressor. We have previously shown that RASSF1C promotes lung cancer cell proliferation and have identified RASSF1C target genes with growth promoting functions. Here, we further report that RASSF1C promotes lung cancer cell migration and enhances lung cancer cell tumor sphere formation. We also show that RASSF1C over-expression reduces the inhibitory effects of the anti-cancer agent, betulinic acid (BA), on lung cancer cell proliferation. In previous work, we demonstrated that RASSF1C up-regulates piwil1 gene expression, which is a stem cell self-renewal gene that is over-expressed in several human cancers, including lung cancer. Here, we report on the effects of BA on piwil1 gene expression. Cells treated with BA show decreased piwil1 expression. Also, interaction of IGFBP-5 with RASSF1C appears to prevent RASSF1C from up-regulating PIWIL1 protein levels. These findings suggest that IGFBP-5 may be a negative modulator of RASSF1C/ PIWIL1 growth-promoting activities. In addition, we found that inhibition of the ATM-AMPK pathway up-regulates RASSF1C gene expression.

Citing Articles

PIWI-interacting RNA (piRNA): a narrative review of its biogenesis, function, and emerging role in lung cancer.

Mukherjee P, Bhattacharjee S, Mandal D Asian Biomed (Res Rev News). 2023; 16(1):3-14.

PMID: 37551397 PMC: 10321162. DOI: 10.2478/abm-2022-0002.

The Role of RASSF1C in the Tumor Microenvironment.

Amaar Y, Reeves M Curr Issues Mol Biol. 2023; 45(2):1113-1126.

PMID: 36826019 PMC: 9954811. DOI: 10.3390/cimb45020074.

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.

Farooqi A, Turgambayeva A, Tashenova G, Tulebayeva A, Bazarbayeva A, Kapanova G Molecules. 2023; 28(1).

PMID: 36615262 PMC: 9822120. DOI: 10.3390/molecules28010067.

Biological effects and regulation of IGFBP5 in breast cancer.

Dittmer J Front Endocrinol (Lausanne). 2022; 13:983793.

PMID: 36093095 PMC: 9453429. DOI: 10.3389/fendo.2022.983793.

Piwi-Interacting RNAs: A New Class of Regulator in Human Breast Cancer.

Qian L, Xie H, Zhang L, Zhao Q, Lu J, Yu Z Front Oncol. 2021; 11:695077.

PMID: 34295823 PMC: 8290475. DOI: 10.3389/fonc.2021.695077.

References

Reeves M, Baldwin M, Aragon R, Baldwin S, Chen S, Li X . RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1. BMC Res Notes. 2012; 5:239. PMC: 3512503. DOI: 10.1186/1756-0500-5-239. View

Vos M, Ellis C, Bell A, Birrer M, Clark G . Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem. 2000; 275(46):35669-72. DOI: 10.1074/jbc.C000463200. View

Reeves M, Firek M, Chen S, Amaar Y . The RASSF1 Gene and the Opposing Effects of the RASSF1A and RASSF1C Isoforms on Cell Proliferation and Apoptosis. Mol Biol Int. 2013; 2013:145096. PMC: 3845702. DOI: 10.1155/2013/145096. View

Pelosi G, Fumagalli C, Trubia M, Sonzogni A, Rekhtman N, Maisonneuve P . Dual role of RASSF1 as a tumor suppressor and an oncogene in neuroendocrine tumors of the lung. Anticancer Res. 2010; 30(10):4269-81. View

Tommasi S, Dammann R, Zhang Z, Wang Y, Liu L, Tsark W . Tumor susceptibility of Rassf1a knockout mice. Cancer Res. 2005; 65(1):92-8. View

Liang D, Dong M, Hu L, Fang Z, Xu X, Shi E . Hiwi knockdown inhibits the growth of lung cancer in nude mice. Asian Pac J Cancer Prev. 2013; 14(2):1067-72. DOI: 10.7314/apjcp.2013.14.2.1067. View

Li J, Wang F, Protopopov A, Malyukova A, Kashuba V, Minna J . Inactivation of RASSF1C during in vivo tumor growth identifies it as a tumor suppressor gene. Oncogene. 2004; 23(35):5941-9. DOI: 10.1038/sj.onc.1207789. View

Dreijerink K, Braga E, Kuzmin I, Geil L, Duh F, Angeloni D . The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc Natl Acad Sci U S A. 2001; 98(13):7504-9. PMC: 34698. DOI: 10.1073/pnas.131216298. View

Gheorgheosu D, Duicu O, Dehelean C, Soica C, Muntean D . Betulinic acid as a potent and complex antitumor phytochemical: a minireview. Anticancer Agents Med Chem. 2014; 14(7):936-45. DOI: 10.2174/1871520614666140223192148. View

10.

Sanli T, Rashid A, Liu C, Harding S, Bristow R, Cutz J . Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells. Int J Radiat Oncol Biol Phys. 2010; 78(1):221-9. DOI: 10.1016/j.ijrobp.2010.03.005. View

11.

Meng X, Li M, Wang X, Wang Y, Ma D . Both CD133+ and CD133- subpopulations of A549 and H446 cells contain cancer-initiating cells. Cancer Sci. 2009; 100(6):1040-6. PMC: 11159162. DOI: 10.1111/j.1349-7006.2009.01144.x. View

12.

Amaar Y, Minera M, Hatran L, Strong D, Mohan S, Reeves M . Ras association domain family 1C protein stimulates human lung cancer cell proliferation. Am J Physiol Lung Cell Mol Physiol. 2006; 291(6):L1185-90. DOI: 10.1152/ajplung.00072.2006. View

13.

Agathanggelou A, Honorio S, Macartney D, Martinez A, Dallol A, Rader J . Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. Oncogene. 2001; 20(12):1509-18. DOI: 10.1038/sj.onc.1204175. View

14.

Estrabaud E, Lassot I, Blot G, Le Rouzic E, Tanchou V, Quemeneur E . RASSF1C, an isoform of the tumor suppressor RASSF1A, promotes the accumulation of beta-catenin by interacting with betaTrCP. Cancer Res. 2007; 67(3):1054-61. DOI: 10.1158/0008-5472.CAN-06-2530. View

15.

Yang L, Chen Y, Ma Q, Fang J, He J, Cheng Y . Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells. Acta Pharmacol Sin. 2009; 31(1):66-72. PMC: 4002693. DOI: 10.1038/aps.2009.177. View

16.

Reeves M, Baldwin S, Baldwin M, Chen S, Moretz J, Aragon R . Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis. BMC Cancer. 2010; 10:562. PMC: 2965177. DOI: 10.1186/1471-2407-10-562. View

17.

Liu L, Yoon J, Dammann R, Pfeifer G . Frequent hypermethylation of the RASSF1A gene in prostate cancer. Oncogene. 2002; 21(44):6835-40. DOI: 10.1038/sj.onc.1205814. View

18.

Burbee D, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B . Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst. 2001; 93(9):691-9. PMC: 4374741. DOI: 10.1093/jnci/93.9.691. View

19.

Siddiqi S, Terry M, Matushansky I . Hiwi mediated tumorigenesis is associated with DNA hypermethylation. PLoS One. 2012; 7(3):e33711. PMC: 3306289. DOI: 10.1371/journal.pone.0033711. View

20.

Hsu Y, Sheu J, Lin C, Yang D, Hsiao G, Ou G . Trichostatin A and sirtinol suppressed survivin expression through AMPK and p38MAPK in HT29 colon cancer cells. Biochim Biophys Acta. 2011; 1820(2):104-15. DOI: 10.1016/j.bbagen.2011.11.011. View