Expression and functional characterization of INPP4B in gallbladder cancer patients and gallbladder cancer cells

Abstract

Background Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines. Methods The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro. Results INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein. Conclusions These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells.

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

“…Inositol 6). Thus, INPP4B is anticipated to act as a tumor suppressor by antagonizing PI3K/Akt signaling (25). Actually, the tumorpromoting features of INPP4B have also been found in several cancers, and it seems that INPP4B plays complex roles in the pathogenesis of different tumors (13,26).…”

“…PI(3,4)P2, like PI(3,4,5)P3, is necessary for the activation of Akt, enhancing tumor cell growth; therefore, INPP4B was hypothesized to be a tumor suppressor protein like PTEN, which dephosphorylates PI(3,4,5)P3(6). Thus, INPP4B is anticipated to act as a tumor suppressor by antagonizing PI3K/Akt signaling ( 25 ). Actually, the tumor-promoting features of INPP4B have also been found in several cancers, and it seems that INPP4B plays complex roles in the pathogenesis of different tumors ( 13 , 26 ).…”

Is the tumor-stroma ratio a prognostic factor in gallbladder cancer?

“…Recent studies have analyzed tumor cells and tumor microenvironments to identify additional biomarkers with a high prognostic and/or predictive value, investigating molecular mechanisms, tumor cell structure, genetic mutations, tumor immune response, and gene expression, although the transcriptomic and genetic data collection in these methods leads to high costs [10][11][12] . The traditional pathological approach to analysis using a microscope is simple, inexpensive, and effective and so a microscopic analysis-based biomarker is desirable.…”

High ATF4 Expression Is Associated With Poor Prognosis, Amino Acid Metabolism, and Autophagy in Gastric Cancer

“…As previously reported (24), wound-healing and Transwell assays were performed to assess the cell migration and invasion abilities, respectively. For the wound-healing assays, GC cells were seeded in six-well plates (6 × 10 5 cells/well).…”