Thursday, December 26, 2024
12/26/2024
PROJECT SUMMARY The activation of signaling tumor cells via the tumor micrenvironment (TME) to undergo metastasis in bladder cancer is understudied. Clinically, increased Col I deposition correlates with bladder cancer progression (i.e. increasing tumor stage). Our published study demonstrated that Col I induces bladder tumor cells to invade and colonize the lung through Discoidin Domain Receptor 1 (DDR1) pathway. Yet, increase Col deposition is known to cause nutrient deprivation which is unsustainable for tumor growth. Tumors can adapt to these increasingly harsh environment by downregulating protein synthesis – a metabolically expensive homeostatic process. Interestingly, this downregulation of protein synthesis has also been shown to promote resistance to anoikis, cell death resulting from extracellular matrix detachment, which cancer cells must overcome when they undergo metastasis. To our knowledge, whether collagen outside-in signaling senses nutrient deprivation and thereafter reduces energy expenditure by attentuating protein synthesis has yet to be investigated. Interestingly, my pilot studies show two independent, yet complementary non-canonical mechanisms of downregulating protein synthesis, which involves Col I-DDR1 interaction. I now propose to 1) interrogate these two mechanisms that downregulate protein synthesis and 2) how this Col I-DDR1 mediated downregulation of protein synthesis affects the efficiency of cancer metastasis. Knowledge gained from the success of this proposal will yield newer insights on Col I-DDR1 interaction in promoting cancer cell survival and metastasis in bladder cancer.
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