New insight into the key proteins and pathways involved in the metastasis of colorectal carcinoma

Abstract

Abstract. Metastasis-associated genomic alterations have been recognized to play a critical role in tumor metastasis. Primary and metastatic tumor cells in mice and tumors in a patient were studied by cDNA array analysis. Selected genes were determined by RT-PCR and immunohistochemistry. Pathways on changed genes were statistically analyzed. The function of Grb2 was determined by in vitro wound assay. Nodal metastatic cells had a stronger ability of growth and metastasis than primary tumor cells. A total of 376 genes showed a different expression between primary and metastatic cells. The expression of Grb2 and genes in the Grb2-mediated pathways was significantly elevated in the metastases. Elevated levels of Grb2 expression in metastases were related to the distant metastasis of colorectal carcinoma. Blocking the Grb2-SH2 domain signaling transduction inhibited cell motility. Metastasis-associated genes identified by cDNA and tissue microarrays provide potentially valuable information on the metastasis of colorectal tumors. Overexpression of Grb2 may contribute to tumor growth, invasiveness and metastasis.

Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance

“…A high frequency of up-regulation of Grb2 and HER2 expression in metastases primary gastric tumors and downregulation of them in primary gastric tumors suggests that Grb2 and HER2 play critical roles in human gastric tumorigenesis and metastasis. This notion is clearly supported by our previous study in colorectal cancer showing that Grb2 and genes in the Grb2-mediated pathways was signiWcantly elevated in the metastases and blocking the Grb2-SH2 domain signaling transduction could inhibit cell motility (Yu et al 2008).…”

“…Moreover, authors have reported overexpression of Grb2 in breast cancer in conjunction with overexpression of SHP-1 (Yip et al 2000); this combined overexpression enhanced downstream signaling through the extracellular signal-related kinase kinase/mitogen-activated protein kinase pathway. Our laboratory once detected Grb2 expression in 35 colorectal cancer specimens through immunohistochemistry of tissue microarray and found that Grb2 was signiWcantly elevated in the metastases (Yu et al 2008). Cheng et al (1998 stressed the importance of Grb2 gene dosage in the onset and development of mammary carcinoma as a possible signal ampliWcation mechanism downstream of active RTKs.…”

Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma

“…GRB2 is critical for cell cycle progression and angiogenesis 45. Blocking the GRB2 signalling inhibits CRC cell motility 46. POSTN has been found to be highly upregulated in CRC tissues and sera of CRC patients 47.…”

Quantitative proteomics reveals the downregulation of GRB2 as a prominent node of F806-targeted cell proliferation network

“…High-expression of GRB2 could promote malignant transformation and progression, and correlate with poor prognosis in several human cancers, such as breast, bladder, gastric and colorectal cancers, suggesting that GRB2 is a potential target for cancer therapy [24][25][26][27]. Moreover, the molecules and signaling pathways that regulate cell proliferation and survival are receiving considerable attention as potential targets for anticancer strategies [28,29].…”