Few areas of the body\u00a0face more daily stress\u00a0and\u00a0potential\u00a0damage than the stomach,\u00a0which\u00a0must\u00a0manage\u00a0everything\u00a0we swallow.\u00a0Along with\u00a0this constant strain,\u00a0the stomach also produces\u00a0acid\u00a0that can\u00a0damage\u00a0its own lining and increase\u00a0the risk of ulcers.\u00a0<\/p>\n
To keep up,\u00a0the\u00a0stomach\u00a0lining\u00a0has remarkably high regenerative rates,\u00a0continuously replacing\u00a0cells and repairing\u00a0damage\u00a0as it occurs.\u00a0This cycle, while essential, activates\u00a0pathways\u00a0linked to\u00a0tumor\u00a0development –\u00a0gastric cancer\u00a0being\u00a0one of the most common and fatal diseases in the world.\u00a0<\/p>\n
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Cancer can develop from abnormal regeneration, so it is vital that the body stops\u00a0the process properly\u00a0and\u00a0restores\u00a0cell identity and function\u00a0in the stomach.”<\/p>\n
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Dr.\u00a0Tae-Hee Kim, Senior Scientist in the\u00a0Developmental,\u00a0Stem\u00a0Cell\u00a0& Cancer Biology\u00a0program, The Hospital for Sick Children (SickKids)<\/p>\n
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“But the mechanisms that regulate tissue restoration have\u00a0long been\u00a0unclear, so we decided to focus on\u00a0this\u00a0puzzle\u00a0in the stomach environment,\u00a0believing it\u00a0may be key to cancer prevention.”\u00a0<\/p>\n
Surprising results lead to new understanding\u00a0<\/p>\n
Members of the\u00a0Kim Lab\u00a0used\u00a0single cell 10x\u00a0multiome\u00a0technology\u00a0available through\u00a0The\u00a0Centre for Applied Genomics\u00a0to study what happens inside stomach cells during healing and recovery\u00a0Together\u00a0with\u00a0the\u00a0Rhee Lab\u00a0at the University of Toronto, they\u00a0analyzed\u00a0the interplay of\u00a0gene expression\u00a0and\u00a0DNA\u00a0regulation\u00a0within\u00a0the same\u00a0stomach cell\u00a0during\u00a0various states of regeneration and recovery.\u00a0<\/p>\n
After\u00a0observing\u00a0unexpected results, the team\u00a0discovered\u00a0the biological processes that regulate gene expression (which specific genes are turned on or off) in\u00a0gastric regeneration,\u00a0recovery\u00a0and cancer. Their study, published\u00a0in\u00a0Developmental Cell,\u00a0highlights\u00a0how certain conditions and responses in the stomach make it vulnerable to cancer.\u00a0<\/p>\n
First, the team\u00a0identified\u00a0that\u00a0the BRG1\/BRM-Associated Factor (BAF) chromatin remodeling\u00a0complex\u00a0is active\u00a0during recovery.\u00a0Inside the BAF complex, they deleted\u00a0Arid1a,\u00a0which is among the\u00a0most altered\u00a0genes\u00a0in gastric cancer, but whose role in regeneration\u00a0and\u00a0recovery is unknown.\u00a0<\/p>\n
“We expected to see\u00a0tumors\u00a0begin to\u00a0form, but that\u00a0was not the case,” says\u00a0Adrian\u00a0Loe, first\u00a0author and\u00a0postdoctoral fellow in the\u00a0Kim Lab. “Instead,\u00a0deleting\u00a0Arid1a\u00a0after an injury to stomach cells left them in a persistent state of regeneration,\u00a0unable to\u00a0recover.”\u00a0<\/p>\n
What this suggests\u00a0is that\u00a0Arid1a\u00a0plays a\u00a0critical\u00a0role in cell recovery in the stomach.\u00a0After weeks of these cells\u00a0remaining\u00a0in\u00a0this\u00a0unresolved regenerative\u00a0(yet cancer-free)\u00a0state,\u00a0the\u00a0researchers\u00a0then removed\u00a0Trp53,\u00a0the most common\u00a0gene\u00a0tied to\u00a0cancer.\u00a0Doing this, in an environment\u00a0marked by\u00a0a loss of\u00a0Arid1a, was sufficient to trigger cancer and cause it to spread.\u00a0<\/p>\n
Exposing the importance of understanding cell recovery\u00a0<\/p>\n
These new findings\u00a0suggest\u00a0that genetic variants tied to cancer are not acting on their own but\u00a0instead depend\u00a0on\u00a0what’s\u00a0happening in the\u00a0surrounding\u00a0environment.\u00a0The study\u00a0shows that\u00a0while the process of regeneration and healing can\u00a0raise the risk of\u00a0stomach\u00a0cancer,\u00a0incomplete recovery\u00a0increases that risk much\u00a0further.\u00a0<\/p>\n
“Regenerative medicine\u00a0is a dynamic\u00a0and fast-moving area of research, but we\u00a0can’t lose sight of the fact that we\u00a0need to better understand how to\u00a0control\u00a0regeneration as well,” Kim says.\u00a0“That’s\u00a0because, as our study showed,\u00a0it opens a susceptibility to cancer.\u00a0<\/p>\n
“As the\u00a0field of regenerative medicine\u00a0advances,\u00a0we\u00a0must also\u00a0focus\u00a0on studying how\u00a0the\u00a0conditions\u00a0that\u00a0return to\u00a0a healthy, balanced state.”\u00a0<\/p>\n
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