PIK3CD induces cell growth and invasion by activating AKT/GSK‐3β/β‐catenin signaling in colorectal cancer

Abstract

The catalytic subunit p110δ of phosphoinositide 3‐kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small‐interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of β‐catenin and T‐cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3β (GSK‐3β) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD‐mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β‐catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with β‐catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK‐3β/β‐catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.

Development of an immune-related gene pairs index for the prognosis analysis of metastatic melanoma

“…Additionally, related researches showed the over-expression of ITGAV was closely related to the development of colorectal cancer and spreading of colorectal cancer cells via perineural invasion 33 . And the high expression of PIK3CD was also proved that affected the distant metastasis and poor prognosis of colon cancer 34 . These studies indicated that the IRGs in IRGPI played an important role in the occurrence and development of cancers, suggesting that our prognostic model would have good prospect and prognostic value in metastatic melanoma.…”

LncRNA HOTAIRM1, miR-433-5p and PIK3CD function as a ceRNA network to exacerbate the development of PCOS

“…Moreover, depletion of PIK3CD also strengthened the positive effect of si-HOTAIRM1 on KGN cells containing increasing cell growth and inhibiting cell apoptosis. Accumulated evidence has shown that PIK3CD was primarily expressed in leukocytes and involved in the development of several hematological malignancies and solid tumors, such as glioma, neuroblastoma, glioblastoma and breast cancer [ 6 ]. However, this is the first time we have reported the function of PIK3CD on KGN cells growth and apoptosis.…”

Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes in head and neck squamous cell carcinoma

“…PIK3CD, whose ectopic expression could affect the biological phenotypes of multiple cancers, was reported to regulate the PI3K signaling pathway [39]. Also, further analysis suggested it could be employed as an independent predictor for the prognosis of cancer patients [40]. Cystic fibrosis transmembrane conductance regulator (CFTR), a gene mainly expressed in epithelial cells, was found to play pivotal roles in both physiological processes and pathological stages [41].…”