Overexpression of immunoglobulin (CD79a) binding protein1 (IGBP‐1) in small lung adenocarcinomas and its clinicopathological significance

Abstract

Immunoglobulin binding protein 1 (IGBP-1) was initially identified as a signal transduction molecule coprecipitating with MB1 (Igα) of the B cell antigen receptor (BCR) complex and was later found to be broadly expressed. Immunoglobulin binding protein 1 has been characterized as an associated and regulatory component of the catalytic subunits of protein phosphatase 2A (PP2A), which is the most abundant phosphatase and plays important roles in cell growth and cell cycle control. The aim of this study was to investigate the expressional characteristics of IGBP-1 and PP2Ac during pulmonary adenocarcinogenesis. The positivity rate of IGBP-1 increased during the course of sequential progression from non-invasive carcinoma (8/30, 26.7%) to invasive adenocarcinoma (37/46, 80.4%) among cases that showed areas of lepidic growth. In contrast, all of the small adenocarcinomas showing a non-lepidic growth pattern were positive for IGBP-1 (20/20, 100%). All cancers that proved ultimately fatal were positive for IGBP-1, and log-rank analysis showed that IGBP-1 positivity was significantly correlated with a poor prognosis. In contrast, atypical adenomatous hyperplasias and lung adenocarcinomas were uniformly positive for PP2Ac. Protein phosphatase 2A was not associated with carcinoma progression. Thus we have demonstrated that IGBP-1 is expressed universally in advanced lung adenocarcinomas, and that its overexpression is significantly related to outcome.

Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy

“…We propose that there is an increase in PP2AC:alpha4 complex formation in cardiac tissue subjected to pressure overload. Interestingly, alpha4 protein expression has been found to be elevated in other non-cardiac tissues undergoing uncontrolled growth [12, 69]. However, an explanation of why alpha4 protein expression was elevated in hypertrophied tissue remains an important question that requires further study.…”

A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling

“…Three translational studies support such a role of the MID1/α4/PP2A complex: (i) a study on colorectal cancer, pointing towards MID1 as a metastatic gene and marker for poor survival [49], (ii) a study, which demonstrated that α4, the direct binding partner of MID1, is expressed universally in advanced lung adenocarcinomas and that its overexpression is significantly related to outcome [50], and (iii) a study, which shows that the expression and activity of PP2A is down-regulated in castration resistant prostate cancer cells [51]. Finally, our present findings and recent reports regarding the crosstalk between MID1/α4 and Akt/mTOR, [15,16,46], two master regulators of essential pathways in proliferation, development, energy balance and immune responses, as well as MID1’s roles in NFκB activation [8] and promotion of Hedgehog signaling [13] stress the multifaceted nature and therapeutic potential of the MID1 complex.…”

The MID1 E3 Ligase Catalyzes the Polyubiquitination of Alpha4 (α4), a Regulatory Subunit of Protein Phosphatase 2A (PP2A)

“…The ␣4-PP2Ac-MID1 complex plays key roles in a variety of cellular processes, including regulating cell cycle progression, cell growth in response to nutrients, and lymphocyte migration (6,11,12,30). Notably, overexpression of ␣4 has been associated with various tumors, including primary hepatocellular carcinomas, breast cancer, and invasive adenocarcinoma (29,30), highlighting the importance of understanding the mechanisms that regulate its levels and function.…”

“…Notably, ␣4 has been found significantly overexpressed in many cancers, including primary hepatocellular carcinomas, breast cancer, and invasive adenocarcinoma (29,30). Furthermore, its ectopic overexpression in immunocompromised mice is sufficient to transform embryonic kidney cells (30).…”