Abstract: The present invention provides a method for the prognosis of overall survival, cancer recurrence or response to treatment for a patient suffering from cancer, the method comprising: (a) examining a sample from the patient to determine whether the patient is human epidermal growth factor receptor 2 (HER2) positive or negative; and (b) measuring WW domain-binding protein 2 (WBP2) levels in the patient's sample, wherein a result in step (a) and a result in step (b) provides a prognosis of overall survival, cancer recurrence or response to treatment for the patient. The present invention also provides a kit carrying out the method of the present invention.

Abstract: The present invention provides a method for the prognosis of overall survival, cancer recurrence or response to treatment for a patient suffering from cancer, the method comprising: (a) examining a sample from the patient to determine whether the patient is human epidermal growth factor receptor 2 (HER2) positive or negative; and (b) measuring WW domain-binding protein 2 (WBP2) levels in the patient's sample, wherein a result in step (a) and a result in step (b) provides a prognosis of overall survival, cancer recurrence or response to treatment for the patient. The present invention also provides a kit carrying out the method of the present invention.

Abstract: The present invention provides a method of predicting response of a cancer patient to a therapy. The method comprises the step of determining a presence or absence of at least one mutation of ITCH (SEQ ID NO: 1) in a first sample isolated from a cancer patient, wherein the presence of a mutation is predictive of response of the cancer patient to a therapy selected from the group consisting of: Wnt pathway-, EGFR-, Her2-, hormonal- and WBP2-based therapy.

Abstract: The invention is directed to non-invasive methods of detecting gastric cancer in an individual in need thereof comprising determining an expression level of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the individual and comparing the expression level to a control, wherein an increase in the expression level of ITIH3 in the individual compared to the control is indicative of gastric cancer in the individual.

Abstract: WW-binding protein 2 (WBP2) has been demonstrated in different studies to be a tyrosine kinase substrate, to activate ER?/PR transcription and to play a role in breast cancer. However, the role of WBP2 tyrosine phosphorylation in regulating ER function and breast cancer biology is unknown. Here, we established WBP2 as a tyrosine phosphorylation target of estrogen signaling via EGFR crosstalk. Using dominant negative, constitutively active mutants, RNAi and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases. We further showed that abrogating WBP2 phosphorylation impaired >60% of ER? reporter activity putatively by blocking nuclear entry of WBP2 and its interaction with ER?.

Abstract: WW-binding protein 2 (WBP2) has been demonstrated in different studies to be a tyrosine kinase substrate, to activate ER?/PR transcription and to play a role in breast cancer. However, the role of WBP2 tyrosine phosphorylation in regulating ER function and breast cancer biology is unknown. Here, we established WBP2 as a tyrosine phosphorylation target of estrogen signaling via EGFR crosstalk. Using dominant negative, constitutively active mutants, RNAi and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases. We further showed that abrogating WBP2 phosphorylation impaired >60% of ER? reporter activity putatively by blocking nuclear entry of WBP2 and its interaction with ER?.

Abstract: Using phosphoproteomics, we profiled the phosphorylation levels of hundreds of proteins concurrently across an isogenic model of breast cancer metastasis. Among them is TRPV4, a calcium channel that we found to be overexpressed in invasive breast tumors compared to ductal carcinoma in situ, a pre-neoplastic lesion and normal tissues. TRPV4 was also found to be elevated mostly in invasive breast cancer cell lines and less so in non-invasive breast cancer cell lines. These data led us to hypothesize that TRPV4 confer early traits of metastatic cancer cells. Functional studies revealed that silencing of TRPV4 expression diminished breast cancer cell migration and invasion significantly but not proliferation. Silencing expression of TRPV4 in metastatic breast cancer cells also reduced the number and size of metastatic colonies in mice. This supports the notion that TRPV4 is an attractive drug target to curb metastasis.

Abstract: Using phosphoproteomics, we profiled the phosphorylation levels of hundreds of proteins concurrently across an isogenic model of breast cancer metastasis. Among them is TRPV4, a calcium channel that we found to be overexpressed in invasive breast tumors compared to ductal carcinoma in situ, a pre-neoplastic lesion and normal tissues. TRPV4 was also found to be elevated mostly in invasive breast cancer cell lines and less so in non-invasive breast cancer cell lines. These data led us to hypothesize that TRPV4 confer early traits of metastatic cancer cells. Functional studies revealed that silencing of TRPV4 expression diminished breast cancer cell migration and invasion significantly but not proliferation. Silencing expression of TRPV4 in metastatic breast cancer cells also reduced the number and size of metastatic colonies in mice. This supports the notion that TRPV4 is an attractive drug target to curb metastasis.

Abstract: Gastric cancer is one of the leading causes of cancer-related death worldwide. To date no specific marker is available for gastric cancer screening. The expression profile of 37 proteins was identified to be consistently different between the plasma of normal and gastric cancer subjects. The expression of complement component C9 protein was validated to be significantly higher in the plasma of gastric cancer compared to normal subjects. This was independent of the gastritis and H. pylori status of the patients. We also observed a statistically significant difference (p<0.04) in the expression level of C9 between patients with intestinal and diffuse types of cancer. Two independent blind test studies showed a high sensitivity and specificity to detect gastric cancer. The C9 protein is a biomarker for screening gastric cancer.

Abstract: WW-binding protein 2 (WBP2) has been demonstrated in different studies to be a tyrosine kinase substrate, to activate ER?/PR transcription and to play a role in breast cancer. However, the role of WBP2 tyrosine phosphorylation in regulating ER function and breast cancer biology is unknown. Here, we established WBP2 as a tyrosine phosphorylation target of estrogen signaling via EGFR crosstalk. Using dominant negative, constitutively active mutants, RNAi and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases. We further showed that abrogating WBP2 phosphorylation impaired >60% of ER? reporter activity putatively by blocking nuclear entry of WBP2 and its interaction with ER?.

Abstract: Gastric cancer is one of the leading causes of cancer-related death worldwide. To date no specific marker is available for gastric cancer screening. The expression profile of 37 proteins was identified to be consistently different between the plasma of normal and gastric cancer subjects. The expression of complement component C9 protein was validated to be significantly higher in the plasma of gastric cancer compared to normal subjects. This was independent of the gastritis and H. pylori status of the patients. We also observed a statistically significant difference (p<0.04) in the expression level of C9 between patients with intestinal and diffuse types of cancer. Two independent blind test studies showed a high sensitivity and specificity to detect gastric cancer. The C9 protein is a biomarker for screening gastric cancer.

Abstract: The invention is directed to non-invasive methods of detecting gastric cancer in an individual in need thereof comprising determining an expression level of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the individual and comparing the expression level to a control, wherein an increase in the expression level of ITIH3 in the individual compared to the control is indicative of gastric cancer in the individual.