The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway.
Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to be crucial during the development and progression of a variety of tumors. However, the role of HPIP in renal cell carcinoma (RCC) is unknown. Here we report that HPIP is upregulated in most RCC patients, positively correlates with tumor size, high Fuhrman grade and preoperative metastasis, and predicts poor clinical outcomes. Mechanistically, we identified casein kinase 1α (CK1α), a critical regulator of tumorigenesis and metastasis, as a novel HPIP-interacting protein. HPIP facilitates RCC cell growth, migration, invasion and epithelial-mesenchymal transition depending on its interaction with CK1α. Activation of mammalian target of rapamycin pathways by HPIP is partly dependent on CK1α and is required for HPIP modulation of RCC cell proliferation and migration. HPIP knockdown suppresses renal tumor growth and metastasis in nude mice through CK1α. Moreover, expression of CK1α is positively correlated with HPIP in RCC samples, and also predicts poor clinical outcome-like expression of HPIP. Taken together, our data demonstrate the critical regulatory role of the HPIP-CK1α interaction in RCC, and suggest that HPIP and CK1α may be potential targets for RCC therapy.
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.|Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
H
H
Mai
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
X
X
Xu
Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
G
G
Mei
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
T
T
Hong
Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
J
J
Huang
Department of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
T
T
Wang
Department of Gynecology and Obstetrics, PLA General Hospital, Beijing, People's Republic of China.
Z
Z
Yan
Department of Oncology, PLA General Hospital, Beijing, People's Republic of China.
Y
Y
Li
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Y
Y
Liang
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
L
L
Li
Department of Thoracic Surgery, PLA General Hospital, Beijing, People's Republic of China.
S
S
Jin
Department of Oncology, PLA General Hospital, Beijing, People's Republic of China.
W
W
You
Department of Thoracic Surgery, PLA General Hospital, Beijing, People's Republic of China.
Y
Y
Ma
Department of Urology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
L
L
Chen
Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, People's Republic of China.
Q
Q
Ye
J Cell Biol. 2007 Jul 30;178(3):437-51
17646396
Onkologie. 2005 Oct;28(10):508-14
16186692
J Exp Med. 2014 Apr 7;211(4):605-12
24616378
Gut. 2008 Jun;57(6):799-806
18203806
Nat Med. 2011 Jun;17(6):708-14
21572428
Lancet. 2016 Feb 27;387(10021):894-906
26318520
J Biol Chem. 2005 Dec 30;280(52):43188-97
16219765
J Labelled Comp Radiopharm. 2015 Nov-Dec;58(13-14):461-8
26503645
Neuro Oncol. 2014 Jul;16(7):946-59
24470547
Cancer Biol Med. 2015 Dec;12(4):342-54
26779371
Mol Cell. 2011 Oct 21;44(2):317-24
22017877
IUBMB Life. 2013 Oct;65(10):873-82
24038948
EMBO Mol Med. 2012 Sep;4(9):952-63
22707389
J Clin Med. 2016 Jan 12;5(1):null
26771648
Med Mol Morphol. 2014 Jun;47(2):63-7
24213520
Sci Rep. 2015 Mar 24;5:9429
25800793
Oncogene. 2015 Aug 27;34(35):4601-12
25486428
Biochim Biophys Acta. 2008 Jun;1783(6):1220-8
18302941
Curr Opin Oncol. 2014 May;26(3):321-7
24675233
J Clin Med. 2016 Jan 27;5(2):null
26828526
Ann N Y Acad Sci. 2015 Jun;1346(1):33-44
25907074
Expert Opin Pharmacother. 2013 Jun;14(9):1229-40
23578333
Breast Cancer Res. 2010;12(3):R30
20507565
J Clin Invest. 2013 Feb;123(2):630-45
23321675
Front Oncol. 2014 May 19;4:96
24904820
J Oral Pathol Med. 2015 Feb;44(2):115-25
25060351
Mol Cancer. 2014 Oct 11;13:231
25306547
Nature. 2011 Feb 17;470(7334):409-13
21331045
Cancer J. 2013 Jul-Aug;19(4):311-5
23867512
Oncogene. 2009 Jan 22;28(3):422-30
18978814
Cancer Res. 2010 Sep 1;70(17):6999-7009
20699366