Mps peptides and use thereof

Abstract

This disclosure provides an isolated polypeptide comprising no more than 35 amino acids, wherein the amino acid sequence comprises, or alternatively consists essentially of, or alternatively consisting of XXXRYSYXXSYX (SEQ ID NO: 1) and equivalents thereof, wherein X is a basic amino acid and Y is a hydrophobic amino acid. Polynucleotides encoding the polypeptides and antibodies that bind to the polypeptides are also provided. Therapeutic and diagnostic uses are further provided.

1 .- 38 . (canceled) 
     
     
         39 . An isolated polypeptide comprising no more than 51 amino acids, wherein the polypeptide comprises an amino acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 2) 
                 
                     
                   KKKRFSFKKSFK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   KKKRFAFKKAFK; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   KKKKKRFSFKKSFKLSGFSFKKNKK; 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   KKKKKRFAFKKAFKLAGFAFKKNKK. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         40 . The isolated polypeptide of  claim 39 , wherein the isolated polypeptide comprises no more than 35 amino acids. 
     
     
         41 . The isolated polypeptide of  claim 39 , further comprising one or more of: an amino acid sequence to facilitate entry of the isolated polypeptide into the cell; a targeting polypeptide or a polypeptide that confers stability to the polypeptide. 
     
     
         42 . A composition comprising the isolated polypeptide of  claim 39  and a pharmaceutically acceptable carrier. 
     
     
         43 . The composition of  claim 42 , wherein the composition further comprises one or more of: phosphate buffered saline, water, emulsions, a stabilizers or a preservative 
     
     
         44 . The composition of  claim 43 , wherein the composition is formulated for administration in an oral tablet, an aerosol, an ointment, a cream, a suspension, a lotion, a powder, a solution, a paste, a gel, a spray, or an oil. 
     
     
         45 . The composition of  claim 43 , further comprising a chemotherapeutic agent or drug. 
     
     
         46 . An isolated polynucleotide encoding the polypeptide of  claim 39 . 
     
     
         47 . A vector comprising the isolated polynucleotide of  claim 46 , and optionally regulatory sequences operatively linked to the isolated polynucleotide. 
     
     
         48 . A method to prevent, reduce, delay, inhibit or suppress solid tumor cell growth or metastasis; promote apoptosis; inhibit cancer stem cell growth; inhibit PIP3 level in the cell; restore sensitivity of a resistant cancer cell to a chemotherapeutic; or suppress tumor cell mobility in a patient in need thereof, comprising administering to the patient an effective amount of the polypeptide of  claim 39 . 
     
     
         49 . The method of  claim 48 , further comprising administering an effective amount of a chemotherapeutic agent or drug to the patient. 
     
     
         50 . A method for restoring sensitivity of a chemoresistant cancer cell to a chemotherapeutic drug comprising by contacting the cell with an effective amount of the isolated polypeptide of  claim 39 , and optionally, wherein the chemotherapeutic drug or agent is a TKI drug or agent optionally selected from cisplatin, paclitaxel, erlotinib or dasatinib; and optionally wherein the chemoresistant cancer cell is a TKI resistant cell. 
     
     
         51 . The method of  claim 50 , wherein the contacting is in vitro or in vivo. 
     
     
         52 . The method of  claim 50 , wherein the tumor cell is selected from the group of a lung cancer cell, a colon cancer cell, a breast cancer cell or a pancreatic cancer. 
     
     
         53 . A method for treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of the polypeptide of  claim 39 , thereby treating the cancer. 
     
     
         54 . The method of  claim 53 , wherein the cancer is selected from the group of a lung cancer cell, a colon cancer cell, a breast cancer cell or a pancreatic cancer. 
     
     
         55 . The method of  claim 53 , further comprising administering to the subject an effective amount of a chemotherapeutic drug or agent. 
     
     
         56 . The method of  claim 53 , wherein the subject in need thereof has a high level of phosphorylated MARCKS levels (p-MARCKS level) in a sample isolated from the subject. 
     
     
         57 . The method of  claim 53 , wherein the subject is a human patient. 
     
     
         58 . A kit comprising the isolated polypeptide of  claim 39 .