HPIP is upregulated in liver cancer and promotes hepatoma cell proliferation via activation of G2/M transition

Abstract

Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has been shown to play a role in cancer development and progression. However, the detailed role of HPIP in cancer cell growth and the exact mechanism by which HPIP regulates cancer cell proliferation remains unclear. Here, we report that HPIP is overexpressed in most of 328 liver cancer patients and regulates hepatoma cell proliferation through G2=M checkpoint activation. HPIP increased anchorage-dependent and -independent growth of human liver cancer cell lines. The amino acid region 531-631 of HPIP was important for its modulation of liver cancer cell growth. The increased effects of HPIP on liver cancer cell proliferation were associated with activation of the G2=M cell-cycle concomitant with a marked increase of cyclin B1 and the inhibition of the negative G2=M phase regulator GADD45a. HPIP knockdown dramatically suppressed the growth of HepG2 liver cancer cells in nude mice. These data highlight the important role of HPIP in liver cancer cell growth and suggest that HPIP may be a good target for liver cancer therapy. V C 2013 IUBMB Life, 65(10): [873][874][875][876][877][878][879][880][881][882] 2013

Hematopoietic pre‐B cell leukemia transcription factor interacting protein is overexpressed in gastric cancer and promotes gastric cancer cell proliferation, migration, and invasion

“…It regulates hepatoma cell proliferation through G 2 /M cell cycle activation and enhances anchorage‐dependent and ‐independent growth of human liver cancer cells. Overexpression of HPIP increases hepatoma cell proliferation, migration, and invasion, and promotes EMT through regulation of mTOR signaling . Similar to upregulation of HPIP expression in breast and liver cancer patients, upregulation of HPIP expression has also been reported in glioma and oral squamous cell carcinoma .…”

“…It is overexpressed in breast infiltrative ductal carcinoma, astrocytoma, and oral squamous cell carcinoma, and promotes cancer cell proliferation, adhesion, and migration . Our recent studies showed that HPIP is overexpressed in liver cancer and promotes hepatoma cell proliferation through activation of G 2 /M cell cycle transition . However, the role of HPIP in gastric cancer is unclear.…”

The interplay between HPIP and casein kinase 1α promotes renal cell carcinoma growth and metastasis via activation of mTOR pathway

“…Recently, accumulating evidence has revealed that HPIP functions as a promoter of the development and progression of cancers, including breast cancer, 2, 3 astrocytoma, 4 liver cancer, 5, 6 oral cell carcinoma, 7 colorectal cancer 8 and so on. However, the role of HPIP in RCC remains unclear.…”

Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study

“…Blocking of HPIP expression can significantly inhibit cell anchorage-dependent and proliferation of human hepatic carcinoma cell 11. Wang et al6 demonstrated that knockdown of HPIP could inhibit thyroid carcinoma cell proliferation, migration/invasion, and epithelial–mesenchymal transition.…”

“…Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) is a novel oncogene that is overexpressed in various human cancers, such as non-small-cell lung cancer,4 human spinal glioblastoma,5 thyroid cancer,6 gastric cancer,7 colorectal cancer,8 breast infiltrative ductal carcinoma,9 oral carcinogenesis,10 liver cancer,11 and human melanoma cell 12. Recent studies have demonstrated the multifaceted role of HPIP in pathways associated with cancer progression, including transformation, apoptosis, invasion, and metastasis 4,6,13,14.…”