MUC1-IκB kinase complexes and their activities
The disclosure provides methods of identifying and making compounds and pharmaceutical compositions containing the compounds that inhibit the interaction between MUC1 and an IKK. The disclosure also provides in vivo and in vitro methods of inhibiting such an interaction. Also embraced by the disclosure are in vitro and in vivo methods of inhibiting the IKK/NF-κB pathway in cells expressing MUC1. The compounds, compositions, and methods of the disclosure are generally useful in the treatment of various cancers, inflammatory (e.g., autoimmune disorders), and transplant rejection.
1. A method of treating a subject having a cancer, the method comprising:
(a) identifying a subject as having a cancer comprising one or more cancer cells expressing MUC1; and
(b) administering to the subject a composition comprising an isolated MUC1 peptide fragment that inhibits the interaction between MUC1 and an IKK, wherein said MUC1 peptide fragment (i) comprises SEQ ID NO:3 or SEQ ID NO:4 and is up to 50 residues in length, or (ii) consists of SEQ ID NO:13.
2. The method of claim 1 , wherein the IKK is IKK-alpha, IKK-beta or IKK-gamma.
3. The method of claim 1 , wherein the isolated MUC1 peptide fragment comprises a fragment of the MUC 1 cytosolic domain, wherein the fragment comprises SEQ ID NO:3.
4. The method of claim 1 , wherein the isolated MUC1 peptide fragment comprises a fragment of the MUC1 cytosolic domain, wherein the fragment comprises SEQ ID NO:4.
5. The method of claim 1 , wherein the cancer cell is from a cancer selected from the group consisting of: lung cancer, breast cancer, colon cancer, pancreatic cancer, renal cancer, stomach cancer, liver cancer, bone cancer, hematological cancer, neural tissue cancer, melanoma, thyroid cancer, ovarian cancer, testicular cancer, prostate cancer, cervical cancer, vaginal cancer, and bladder cancer.
6. The method of claim 1 , further comprising delivering one or more additional anti-cancer therapies.
7. The method of claim 6 , wherein the one or more additional anti-cancer therapies comprises one or more chemotherapeutic agents, one or more forms of ionizing radiation, or one or more forms of hormonal therapy.
8. The method of claim 1 , wherein the subject is a human.
9. The method of claim 1 , wherein the subject is a human.
10. The method of claim 1 , wherein the isolated MUC1 peptide fragment consists of SEQ ID NO:13.