HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion

Abstract

Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP) was shown to play a role in cancer development and progression. However, the role of HPIP in colorectal cancer (CRC) is unknown. Here, we report that HPIP is overexpressed in most of CRC patients and predicts poor clinical outcome in CRC. HPIP promotes CRC cell proliferation via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. HPIP inhibits CRC cell apoptosis accompanied by the decreased levels of BAX and PIG3, the inducers of apoptosis, and the increased level of the apoptosis inhibitor BCL2. HPIP blocks caspase-3-mediated cleavage of PARP, an important apoptosis marker. HPIP promotes CRC cell migration and invasion, and regulates epithelial-mesenchymal transition (EMT), which plays a critical role in cancer cell migration and invasion. Activation of MAPK/ERK1/2 and PI3k/AKT pathways is required for HPIP modulation of CRC cell proliferation, migration and EMT. Moreover, HPIP knockdown suppresses colorectal tumor growth in nude mice. These data highlight the important role of HPIP in CRC cell proliferation and progression and suggest that HPIP may be a useful target for CRC therapy.

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

“…Some studies have inferred that HPIP can mediate specific estrogen receptor signaling in several cancer cells 13,14,20,21. Feng et al8 speculated that HPIP could activate MAPK/ERK pathway in colorectal cancer cell, thereby promote tumor proliferation and migration 8. These research studies provide important information that demonstrates the mechanism by which HPIP contributes to carcinogenesis and tumor development.…”

“…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.…”

“…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. HPIP can promote cell growth by inhibiting apoptosis and activation of cell cycle progression, accompanied by changes in expression of apoptosis and cell cycle regulators 8. However, the biological significance and clinicopathological role of HPIP in EOC remain unclear.…”

Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib

“…For apoptosis analysis, cells were labeled with 7-aminoactinomycin D and fluorescein isothiocyanate- Annexin V by following the manufacturer’s instructions (BD Biosciences, Franklin Lakes, NJ, USA). Then, cells were collected and analyzed by a FACS Calibur Flow Cytometer (BD Biosciences) 17,18…”