Upregulation of AKIP1 contributes to metastasis and progression and predicts poor prognosis of patients with colorectal cancer

Abstract

BackgroundA kinase-interacting protein 1 (AKIP1) has been reported to play an important role in the development and progression of cancer. However, the clinicopathological and biological roles of AKIP1 in colorectal cancer (CRC) remain largely unknown. The aim of this study was to investigate AKIP1 protein expression in CRC and determine the correlation between AKIP1 protein expression and clinicopathological features, as well as prognosis in CRC patients.Materials and methodsAKIP1 protein expression was determined by immunohistochemical analysis using tissue microarrays of CRC. We also used an siRNA approach to knock down AKIP1 expression and determine the effect of AKIP1 on CRC cell migration by transwell analysis.ResultsAKIP1 expression in CRC tissue was significantly higher compared with that of noncancerous colorectal mucosa (P<0.001). Further analysis showed that AKIP1 expression was significantly associated with tumor diameter, TNM stage, and lymph node metastasis (P<0.05). Kaplan–Meier survival analysis demonstrated that patients with a positive AKIP1 expression had significantly poorer overall survival rates when compared with those with negative AKIP1 expression (P=0.031). Multivariate analysis using the Cox proportional hazard model, however, revealed that AKIP1 expression was not a significant independent prognostic factor for CRC. Transwell assay showed that the migration potential of si-AKIP1-transfected cells was significantly reduced when compared with control cells.ConclusionElevated AKIP1 expression may contribute to metastasis and progression of CRC. Moreover, high AKIP1 expression in CRC significantly correlated with a patient’s shorter survival time. Therefore, AKIP1 may be a useful prognostic marker for CRC and a promising novel target for the treatment of CRC.

A‐kinase interacting protein 1 might serve as a novel biomarker for worse prognosis through the interaction of chemokine (C‐X‐C motif) ligand 1/chemokine (C‐X‐C motif) ligand 2 in acute myeloid leukemia

“…Recent studies reveal that AKIP1 has potential to be a prognostic marker in several solid cancers . For example, AKIP1 serves as a mediator of tumor metastasis, and its high expression is correlated with unfavorable prognosis in patients with non‐small cell lung cancer .…”

“…For example, AKIP1 serves as a mediator of tumor metastasis, and its high expression is correlated with unfavorable prognosis in patients with non‐small cell lung cancer . In another study AKIP1 is an independent predictive factor for decreased accumulating OS in patients with colorectal cancer . As for CXCL1/CXCL2 are found to be of prognostic value in various cancers including hematologic malignancies, and their involvements in leukemia have been illustrated by several studies .…”

“…Accumulating researches indicate that AKIP1 dysregulation is associated with pathological conditions, and AKIP1 participates in the development and progression of various types of solid tumors. [5][6][7] For example, clinical experiments in patients with gastric cancer illustrate that AKIP 1 high expression correlates with advanced TNM stage and lymph node metastasis, and mechanistic experiments exhibit that AKIP1 promotes gastric cancer cell proliferation, migration, and invasion by activating slug-induced EMT. 5 Another study displays that increased AKIP1 expression is associated with early recurrence and AKIP1 is a potential mediator of tumor metastasis via regulating Wnt/β-catenin signaling in hepatocellular carcinoma.…”

“…AKIP1, A-kinase interacting protein 1; AML, acute myeloid leukemia; CXCL1, chemokine (C-X-C motif) ligand 1; CXCL2, chemokine (C-X-C motif) ligand 2; and EFS, event-free survival Recent studies reveal that AKIP1 has potential to be a prognostic marker in several solid cancers. 6,17,18 For example, AKIP1 serves as a mediator of tumor metastasis, and its high expression is correlated with unfavorable prognosis in patients with non-small cell lung cancer. 18 In another study AKIP1 is an independent predictive factor for decreased accumulating OS in patients with colorectal cancer.…”

“…A‐kinase interacting protein 1 (AKIP1), a molecular regulator of protein kinase A, is reported to serve as an adaptor or structural intracellular protein and is localized to the cytoplasm, nucleus, and mitochondria . Recent studies reveal that AKIP1 contributes to the tumorigenesis angiogenesis, lymph angiogenesis, and invasiveness in several solid tumors, including breast cancer, colorectal cancer, and gastric cancer, and it predicts worse survival profiles in patients with cancer, suggesting that AKIP1 functions as an oncogene and may be an effective prognostic marker in these cancers . Whereas in hematologic malignancies, the role of AKIP1 is limitedly studied.…”